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The Emissary Movie

The Emissary MovieHere is a movie my husband and I have been working on producing, featuring Door County, aliens, mindfulness, The Edmund Fitzgerald, radioactive cheese curds, and a time bomb from outer space.

About a year ago I started updating a randomly selected chapter from my book. I thought, I'll just start with the plants that grow locally, to narrow it down! Well, just one chapter took over a month of work. Exhausted, and now busily working on the novelization of our science fiction comedy movie, The Emissary, this project remains on the back burner for now. But it is shame for this doc to sit on my desktop unread, I realized. It feels wrong to work really hard on a project and not share it, so here it is!

If you ask most people, their first experience with formaldehyde arose in high school biology. Perhaps you recall biological specimens ominously afloat in jars of stinky liquid. (Formaldehyde is actually a gas, not a liquid, but because gasses are so inconvenient to deal with what with their flying around a room uncooperatively, formaldehyde is usually dissolved in water to make it more compliant—and if it is around 10% to 30% this mixture is then called formalin.) Or if you are like me, you associate formaldehyde with the smell of embalming fluid if you have spent any time hanging around cadavers (sometimes I teach anatomy).

Now what surprised me in researching formaldehyde was just how many modern products contain or release it, from cosmetics to building materials and even some common, chemically-treated forms of cotton, wool, and silk—what I'd presumed was "natural" fabric. The word "formaldehyde" does not appear in the ingredients list of any cosmetic that I am aware of, and I'd be startled to find it there. However, many lotions, hair products, deodorants, and other cosmetics contain preservative molecules that react to become formaldehyde, known as formaldehyde releasers. I have a list of these releasers below. (You could always copy the list to bring it to the store with you the next time you go shopping, to squint endlessly at ingredient lists to find them, as I now do. Think of it as a sort of un-treasure hunt.)

What you don't know can hurt you.

Exposing yourself and your family to formaldehyde in apparently benign consumer products is worth thinking about. This is because of excellent, what scientists like to call rigorous, evidence that formaldehyde causes, at best, contact dermatitis, allergic reactions, and rashes, and at worst, cancers like leukemia. You can bore yourself, as I have, reading lots of published, peer-reviewed, epidemiological and laboratory studies in reputable science journals to confirm there's sound evidence for this. Now, I don't think we need to panic, but it does make sense to educate ourselves and to limit our exposure to formaldehyde. That's just smart. We can also put pressure on companies to please sell us healthier alternatives, even if we (meaning me actually) are scared that some of them might snipe back with accusations that we are anti-business or that we are unpatriotic.

The real reason why a molecule is bad for you—it's never about where it comes from.

First of all, if you look around on the Internet at all the various sources of information and misinformation about whether or not formaldehyde is actually that bad, you could easily get confused. This is because we habitually judge molecules based on where we find them, rather than what they do, and my point is that this is a bad habit. This confuses everyone! People are always asking, "where did you get that molecule?" as if the original habitat of a molecule haunted it throughout its existence, and provoked it into good or bad behavior. Formaldehyde is found in cells, in plants, in our bodies, even in floating about in outer space, plus we can make it in a lab if we want to. Does this make it good or bad?

All formaldehyde molecules are identical, by the way. All formaldehyde molecules have one carbon that is attached to two hydrogens, and that one carbon is also attached to an oxygen by something called a double bond. These four atoms, when attached in this manner, are the whole thing. It is a tiny, inanimate object, without a memory or a motive, and, regardless of its origin, all formaldehyde molecules are the same and have this structure:

Stay with me here, I really do have a point with all this boring if-it-has-four-atoms-connected-in-this-exact-structure-it's-formaldehyde chemistry lecture.

It came from my body so it can't hurt you...?

Now, part of my researching formaldehyde and other molecules inevitably gets dragged down by running into a sort of disinformation campaign. It is one that tries to convince you that a molecule isn't really that bad because "it's found in your own body" or that it is "found in plants". Or you'll hear that it is bad because it was made in a nasty lab by nasty humans (even though humans are only extra-smart animals and thus a frighteningly integral part of nature, too.) What makes the Origination-Determines-Goodness argument even more confusing is that molecules found "in nature" are in every way identical to what we make in a lab if we want them to be. All you have to do is have the same connections of the same atoms, and it is the same molecule! A lab-made molecule behaves the same way as one extracted from the environment in every conceivable test as long as this is true. This has been proven unambiguously, repeatedly, since the first organic molecule was synthesized in 1828. (This was the molecule urea, which is found in your own body—it's in urine.)

People get very emotional about where a molecule comes from, too, and that makes me scared to recount the facts, sometimes. At one talk I even had a passionate audience member drag me aside afterwards to try to convince me that a person's intention of making a molecule, either for profit (bad) or to heal (good) affects the molecule's goodness. This notion sounds too mystical for me to imagine how you could go about scientifically testing it. Lots of money is at stake in selling, promoting or demoting and demonizing various molecules based on where the molecule comes from. But I feel I must address this repeatedly simply because it comes up repeatedly: What is most instructive to ignore where we find a molecule and just see what it does.

For example, the oil and chemical industry billionaire Koch brothers, whose companies incidentally profit from selling products that release formaldehyde, employ lobbyists who petition the EPA with reassuring statements like "formaldehyde is found in all organic life forms" (so are there other types of life forms? If so, please tell me about them!), and that "it does not accumulate in the environment".

But as you will soon see, formaldehyde doesn't accumulate in the environment because it is so unstable, it transforms into something else upon reacting with your tissues before it has time to do anything else like accumulate. Koch Industries also employs lawyers to complain about the un-American and anti-business-minded nature of any writer who quibbles with their pro-formaldehyde stance so maybe I had better watch myself here and keep to the topic.

This argument—that something isn't that bad because it is found in your own body—always makes me want to pound my head on my laptop. Our bodies also naturally make poo. And although E. coli is in my own body, and I will not suggest it is benign or that we should all bathe in it. Enough said.

Unfortunately we seem to be stuck in an old fashioned mind-set of judging the worth of a molecule by where it comes from, which is interesting, but rarely helpful. Nature makes both rash-inducing irritants and nourishing vitamins in the same plant. We know that we ought to judge people by how they behave, not where they are from, otherwise we are bigots and not very smart. We should do the same for molecules. Good questions to ask a molecule are, "Are you too stable or too unstable? Do you impersonate other key biomolecules? Do you play well with other molecules or do you destroy them randomly? How do you behave in children, animals, men, women, and the environment?"

How to think like a toxicologist: a molecule's structure and stability is key.

The toxicity of a molecule really does not have anything to do with where it comes from, even though some sources, like snake venom, are more reliable sources of toxins than others. The toxicity of a molecule often has to do with its structural stability, which is dependent on the arrangement of its atoms. Some molecular structures are more stable than others. Why is stability important?

If you live next to an unstable neighbor, you might worry, for example. An unstable neighbor could be is more likely to play with explosives in their garage, or put weird things in your garden, and it does not matter what country they come from. Stability is not the only reason for a molecule's actions—sometimes molecules engage in identity theft, so to speak, impersonating other similar-looking molecules in your body, which can actually be either good or bad depending on the situation. But toxicity always has to do with a molecule's appearance, it's structure, not where it is from. That's why I was going on about how "one carbon's attached to an oxygen and two hydrogens" in formaldehyde. It's important.

A molecule's bonds should be neither too stable nor too unstable.

Molecules have to have the right sort of stability to be benign. If they are too stable, organisms can not break them down easily, and they persist in our neighborhoods. This is only a problem if they also happen to be toxic, like PCBs, which have a structure similar to steroid hormones, and impersonate them, which ends up causing serious problems in a cell. So, it's good for molecules to be able to neatly break down and get recycled by cells of some sort of organism. However, some unstable molecules break down in a messy way that causes damage to other molecules near them. Formaldehyde is one of these, breaking down in a messy way, that like an explosion, hurts other innocent bystander molecules.

What determines stability has to do with what atoms are attached, and in what way. Some sorts of connections between atoms are more stable than others, and chemists learn how to recognize patterns that are either stable or unstable based on some simple rules. (If you can ever get through the grueling process of your first chemistry class, which I think is honestly the hardest chemistry class anyone can take, organic chemistry is next, which teaches you to recognize these simple patterns, and it is so much easier and more fun!)

The sad story of formaldehyde's naked, sticky carbon (warning: chemistry ahead. You can skip this section if you are in a hurry, but you are smart enough to understand it!)

The real reason why formaldehyde is bad for you is because the molecule is unstable, just like a two-legged chair is unstable. It doesn't matter where you find the two-legged chair, whether you buy it from a factory or make it by hand or if you happen to find it on Mars. If the chair has only two legs it will fall over when you sit in it.

1) Formaldehyde is unstable because the single carbon atom in it has what chemists call a strong "partial positive" charge. This isn't as positive as +1, but it isn't zero, either—you could imagine it as something like +0.5 but it's actual value is less important than the fact that it is not zero. For some reason (we actually don't know why!) nature predictably loves charges to be as close to zero as possible. We never see charges as high as +25 just hanging around in any object, for example. That would be very unstable and nature would find a way to mix that ridiculously positive charge up with any nearby negative charges to neutralize it, or nature would spread that large charge out over large area to make it the charge less localized and dense in one small region. We may not know why nature loves charges to be zero, but we can make fantastically good predictions about the behavior of charged things knowing that's the case.

That being said, some atoms comfortably tolerate small positive or negative charges and may even "prefer" (be more stable) to have charges on them (this is based on esoteric geometrical things like the atom's size and the distance from their positively charged centers to their negatively charged outer electron clouds.) But carbon just isn't one of those atoms that tolerates even a fractional charge.

The reason why this carbon has this strong partial positive charge in the first place has to do with its double bond to oxygen. Oxygen always pulls negative charge away from any carbon that it is directly bonded to, making the carbon less negative and therefore more positive (and if you want to know why oxygen does this, I'd have to tell you about something called electronegativity and risk losing the focus of this article.) In my mind this partial positive charge on carbon makes the carbon reactive or "sticky".

2) Now, not only is this carbon "unhappily" partially positive, but unlike most carbons in other compounds, it doesn't have much near it to physically block the approach of something negative that could neutralize its unstable charge. Most carbons in other molecules have bigger, bulkier atoms attached to them, like other carbons. Not only is formaldehyde's carbon sticky, but it is kind of naked, too. You can't see this in the structure above, but hydrogen atoms are the smallest of all the atoms, and the two teeny tiny hydrogen atoms bonded to the carbon are not big enough to physically shield the carbon from the interest of something that it could bump into and could bond with it.

The stability of massive objects like two-legged chairs is dependent mainly on the Law of Gravity. Since molecules don't weigh much, their stability is instead dominated by another natural Law: Nature's tendency to make charges as close to zero as possible, otherwise known as the Electrostatic Law. This second law, in my mind, explains almost all chemical phenomena, which is saying a lot.

There is a reason why formaldehyde preserves tissues. Remember that formaldehyde's unstable carbon "wants" to be stabilized by something negative? In biological tissues, the negative thing it will most likely to encounter is something called an amine. An amine is just a particular pattern of atoms commonly found around a nitrogen atom, and you can depend on that nitrogen to have negatively charged particles called electrons hanging out on it because that is always part of how an amine's structure is defined. Amines are abundant in living things, as you can reliably find them in proteins and DNA.

So, formaldehyde reacts with both proteins and DNA. More precisely, formaldehyde's carbon yanks on the amine's electrons and turns them into a strong bond, which helps carbon have a charge closer to zero. The remnants of the formaldehyde molecule remains unstable, so continues to self-destruct and eventually welds itself onto a second nearby amine. This bonding is the real problem.

Formaldehyde ties together proteins to other proteins, and occasionally to DNA too. This action is termed crosslinking. Crosslinking renders the fraction of vulnerable proteins and DNA that the formaldehyde was in direct physical contact with permanently dysfunctional or useless. If you were a protein, imagine you get some gigantic object permanently stuck to your hand. That would make you less able to perform your regular activities too, right?

Not only does this crosslinking stiffen and toughen the tissue and make it less likely to break down, it also makes too tough for bacteria that would like to eat it and decompose it, and formaldehyde tends to kill those bacteria, anyway, because it does the same thing to their proteins. That's why formaldehyde preserves tissues—nothing left alive can eat much of what is left of the tissues. The residual sugars, water, and small molecules remain encased in a gooey matrix of toughened, crosslinked proteins.

This crosslinking is all fine and good for tissue that's already dead, but what about having this activity going on in our own living tissue? Dysfunctional and useless proteins and DNA in our bodies? Should we panic about that? It depends.

Now, it isn't necessarily the end of the world if some of your protein or even your DNA is mechanically abused this way—it happens every day in the wear and tear of normal aging and we have evolved wonderful enzymes that zip around, repairing or breaking down and recycling our damaged molecules. (Yes, cells recycle. How about that! I am always reminding my students that cells have survived on earth for billions of years, so if we have any smarts we should copy this obviously brilliant energy strategy. Even our grandparents knew how to re-use things. But I digress...) So, our bodies can repair molecular damage to some extent. However, not all DNA damage is the same--some is harder to repair. Crosslinking is hard to repair.

Adducts Cause Cancer

This cross-linking form of damage involves the formation type of bond (called covalent) that is especially tough to break. The unwelcome addition to our newly appendaged molecule is called an adduct (pronounced ADD-uct). Literally an adduct gets stuck to valuable molecules and it won't come off, so those molecules malfunction. (Well, to be technically correct, the formaldehyde reaction is considered reversible and you could break the adduct off if you want to heat it to 203 F (95 C). But because it is insane to burn yourself this is not a practical consideration unless you are talking about doing that reversal in a test tube.)

My pulse quickens when I read about molecules forming adducts to DNA because that is usually bad news and the first thing I think is, "oh, oh, that could be carcinogenic". Adduct-forming molecules often are. (In researching the herb valerian for my book Herbs Demystified, for example, I was concerned to learn that this plant contained a molecule with an unstable bond called an epoxide. Epoxides form adducts and some are carcinogenic. However, there does not appear to be an association of valerian consumers with cancer that is statistically obvious, perhaps because valerian's epoxides may degrade too quickly to cause harm.)

Examples of known carcinogen molecules that form adducts are found in tobacco smoke, burned meat (polyaromatic hydrocarbons and nitrosamines), fungal toxins (aflatoxin), certain pesticides (lindane) and even (weakly) estrogen. Even some simple elements form adducts, too, like mercury, lead, and arsenic. Some are more effective at forming adducts than others, and although our body can repair some adduct damage, obviously less exposure to adduct-formers is a good idea. The more you expose yourself, the more you roll the dice to get a cancerous cell. Why does this cause cancer, though?

Typically one or two permanently damaged DNA molecules doesn't cause cancer, but the more you damage, the greater the risk of cancer. DNA provides instructions for making a protein, so if you mess up these instructions you get eventually get a dysfunctional protein. What happens is that eventually you get a protein that malfunctions in that it fails to turn cell division off (the cell's brake gets stuck in the off position), or it malfunctions in that it continuously turns cell division on (the cell's accelerator gets stuck in the on position.) Either way, you get a continuously dividing cell, which turns into a mass of dividing cells called a tumor. And guess what! Formaldehyde is officially considered carcinogenic. It is most associated with "blood cancers", that is, cancers of white blood cells like leukemia. Lots of unhappy lab animals have proved that. People who work with formaldehyde in industry are statistically more likely to get leukemia, too.

If you just expose your skin to it or breathe it in (remember, it's really a gas) it will do some limited crosslinking of proteins in your skin and respiratory tract. So it's not surprising that it is well known to cause contact dermatitis, rashes, and irritation. Since this attracts the attention of your immune defense system, it is common to develop an allergy to it.

Some natural fabrics are more natural than others.

I'd always felt a bit righteous buying "100% cotton" but now I've reconsidered how I purchase my family's knickers. One of my dear friends, fiber artist and fashion designer Peter Ciesla of Bazyli Studios in Baileys Harbor, Wisconsin, recently complained that after years of professional sewing, he will no longer work with certain fabrics because of painful rashes on his hands. From now on, he said, he was doing only organic fabrics, or vintage recycled ones. "What sorts of fabrics have been hurting you?" I asked, my inner toxicologist anticipating a list of weird new synthetics. I was very surprised when he said his problem was with certain cottons, silks, and wools. What?

Convenience vs. rashes, it's up to you.

It turns out that, in the 50's, our desire to avoid wrinkly fabrics inspired the creation of chemical solutions that crosslink our textiles into a more compliant state. Originally formaldehyde was used. Now formaldehyde is still used, though there is less of it in modern commercial resins, with some companies like BASF even promoting an "eco" version resin with lower formaldehyde called "eco fixapret". Yet anything that is "permanent press", "easy wear", or "wash and wear" is likely to release some irritating substance which, if not formaldehyde, is related to it structurally, and will work in the same irritating manner.

Are you allergic to your clothes?

Formaldehyde and its releasers are the most common cause of contact dermatitis. This is according to the riveting textbook Practical Contact Dermatitis (1995, Guin), which has a whole chapter devoted to formaldehyde! If you get a rash where your clothing contacts your body closely, this text proposes it's likely formaldehyde is to blame. Do you handle a lot of clothing in your profession? My poor friend Peter's textile version of formaldehyde allergy arose after years of fingering formaldehyde releasing fabrics as a professional fabric artist. Also, this dermatology text advises if you get rashes where you sweat, since damp fabric clings more to your skin, this text suggests formaldehyde in the fabric is the culprit. Solution: tolerate wrinkly non-permanent press clothes or buy an iron. Remember those things?

Permanent press hair is now available and is causing the same problems.

Sophie Uliano, author of the fabulous reference Gorgeously Green, suggested I investigate the use of formaldehyde in the latest trend, a hair-straightening procedure, memorably trademarked a "Brazilian Blowout". It's also called keratin hair straightening, and is apparently immensely popular for women who just want their hair straight. Even though it only lasts about three months and costs a pretty penny, some women who can afford it love it, and have it done regularly. However, there are also plenty of women complaining about how it has caused rashes and even serious breathing problems following the procedure.

Intimidated by beauty salons, I'll confess I shy away from them, trimming my own hair the low tech dorky way (admittedly badly) with scissors and a mirror. So I knew nothing about this procedure, of course. And when I told my husband that I needed to learn about Brazilian Blowouts he perked right up and waggled his eyebrows suggestively at me. He didn't know what it was, either. We are both dorks.

I was in luck because our peninsula is now abuzz about a brand new ecological beauty salon opening in Egg Harbor, Wisconsin, Spa Verde, conveniently next to our local health food store, Greens N' Grains. And I just happened to know the lovely stylist managing the salon, Andria Nikoupolis-Weliky, so I thought she'd be the perfect person to ask about this procedure.

Andria said she felt compelled to open the salon because she felt so worried about the health risks from exposure to common salon products that she had herself used for years. I have no experience with nail products, because I play the harp and trim my nails down to oblivion to prevent unpleasant string clicks. Yet I do have friends with beautified nails that continually irritate them. Andria informed me that several brands of nail polish are particularly problematic for women. Andria said her salon uses alternative polishes that don't have formaldehyde or their releasers. So, healthier options for nails are available.

I asked Andria what she would do if a woman came into her salon and asked for this Brazilian Blowout, or keratin straightening, or whatever you want to call it. She said she would partly counsel the woman to find out what she really wants. It would be a lot easier to start with someone who was comfortable with whatever hair type they already have, she confided. She would encourage the person to learn to be comfortable with who they are and the hair they were born with. But if this sort of personal counseling failed, and a curly-haired woman insisted on having straight hair, Andria would be honest with them and tell them their ecological options. She'd use traditional and non-toxic methods like a flattening iron and non-toxic hair care products—which would need to be repeated after every shampoo.

So, more work would be involved, just not unlike non-wash-and-wear clothing. But here is how I think about it: it may be less work to use a flattening iron every day than to cure yourself of leukemia, or even deal with painful rashes and breathing problems, in the long run. And learning to cherish whatever hair type you were born with is maybe not such a bad thing.

There is confusion about whether or not some of these keratin straightening procedures have more formaldehyde than others, and some even claim to not have any. Again, the problem is similar to the wash-and-wear clothing. In order for the procedure to work, you need a chemical reaction that involves either formaldehyde or molecules that have structures that work similarly, which is the root of what causes the rashes in the first place.

Formaldehyde in cosmetic products

I was out shopping and pondering formaldehyde, and coincidentally ran into my dermatologist, Dr. Diane Thaler. I used that opportunity to probe her knowledge of the chemical. She surprised me by revealing that it was indeed in several cosmetic products, causing her to change brands of shampoo during medical school, because the formaldehyde-containing ones made her head itch uncontrollably.

Wait a minute! I thought. I am an obsessive label reader. But I didn't remember ever seeing a bottle of shampoo or lotion or any sort of cosmetic product with "formaldehyde" on the ingredients list. That would be like seeing the word "carcinogen" on the label. I would have remembered that! What was going on?

When formaldehyde-free isn't

Diane's helpful references led me onto the trail of "formaldehyde releasers". They are not formaldehyde, but because they break down and release formaldehyde over time, they, like formaldehyde, increase the shelf stability of the product. That is how a product can expose you to formaldehyde and not have formaldehyde on the label. Quaternium 15, for example, is one of these, and according to my contact dermatitis textbook, it's the most common cause of contact dermatitis found in cosmetic products.

Here's a list of common formaldehyde releasers:

para-formaldehyde

hexamethylene tetramine

DMDM hydantoin

polynoxyline

dimethylolurea

preventol D1

preventol D2

preventol D3

quaternium 15

bakzid

bakzid P

parmetol k50

grotan BK

imidazolidinyl urea

diazolidinyl urea

2-bromo-2-nitropropane-1,3-diol

KM 103

biocide DS 5249 (Proxel T)

tris hydroxymethyl nitromethane (Tris nitro)

hydroxymethylglycinate (Suttocide A)

Now, I sympathize with the desire to use preservatives, but there are smart ways of doing this, and not so smart ways. My first attempt at creating hand lotions in order to promote a local artist's work--her art was on the label--failed. I thought that vitamin E would preserve the product, but I should have added more, and perhaps used an additional backup. It turned out my all-natural ingredients were so yummy to various airborne fungi that several of the containers were quickly colonized with fuzz. I had on hand many all-natural petri dishes. I had to toss them. Damn those microbes, for they must have had a ball feasting upon all that expensive organic shea butter.

But there are ways to make products less appetizing to microorganisms by playing with more variables, and I am sure I didn't need a formaldehyde releaser to do the job. You can start by making a cosmetic product too acidic, too basic, too minerally, too dry, or too salty for most microbes to want to live in it, for example. Some "natural" cosmetic products are also preserved by pungent plant oils, although these can be just as irritating to your own cells as to microbial ones, though, because the mechanism works the same way on both cells (fragrant molecules called terpenes tend to dissolve cell membranes). If you have sensitive skin, it really does make sense to avoid even "natural" fragrances. Like I've said before, the origin of a molecule doesn't determine it's behavior.

How to reduce formaldehyde in your home—use green alternatives.

The most common source of formaldehyde in homes is from certain adhesives used in pressed wood products. The glue is either a formaldehyde-urea or phenol-formaldehyde resin. MDF, or medium density fiberboard, has the most resin per wood, and is therefore the worst offender. Other formaldehyde releasing materials include particleboard, hardwood plywood paneling, softwood plywood, and flake or oriented strand board.

Formaldehyde in buildings hit the media radar after thousands of residents of FEMA trailers inhabitants complained about difficulty breathing, asthma, and allergic reactions. About 83% of the trailers were found to have formaldehyde concentrations greater than what the EPA recommends.

Luckily, consumer demand has made widely available—as in your local Home Depot or other big box store—building materials made with alternative glues that don't release formaldehyde. As always, look at the label and do a little research before you buy. The more alternatives we demand and purchase, whether it is plywood, shampoos, or clothing, the more industry will listen and profit, and no one will get hurt.

A dear friend of mine was recently diagnosed with rheumatoid arthritis, and wrote me:

Dear Holly,I was just thinking of you and wondering how you are doing. I also was wondering if you would mind checking some thing out that some friends informed us about. It is a product called max GXL. It helps with the production and preservation of Glutathione which I have never heard of. There is an interview with the man who came up with it that I thought you might find interesting. I am very curious what you think. The web-site is (edited out by me)

Here's my reply:

That is funny, I did my graduate research on glutathione, which is a natural antioxidant made of three amino acids bonded together, found in all of our cells. I was trying to invent new drugs that increase it.

So I can tell you all about that, I got my PhD on the topic. And yes, I think glutathione is a wonderful thing!!! It is depleted in many diseases and also helps our bodies get rid of toxins, as well as being a general antioxidant. But don't buy it from that company. They are charging way too much, and in my opinion taking advantage of sick people. Over 60 bucks for less than a months supply of pills? Slimeballs!

I HATE it when supplement companies take advantage of sick people.

Not everyone needs to increase glutathione. Actually, I don't think taking supplements that boost glutathione will do a thing unless you are depleted of glutathione in the first place. That is what we find when it comes to taking antioxidants in general. But in your case it can't hurt to try something that will ensure your glutathione levels are up to normal. We find that glutathione is depleted in many chronic diseases and in cases of acute and long term poisoning. In those cases, increases glutathione to normal levels does help!

You can't really boost glutatione above normal, without it being recycled, but you can increase to normal levels that were depleted. (Of course, also keep up with your regular treatment of a healthy diet and lots of exercise!)

For a while I had a miserable job of poisoning hundreds of mice with acetaminophen ("Tylenol"), and then saving a portion of them form dying a horrible death of liver failure with either new drugs that I had synthesized or a standard treatment that boosts glutathione (called "NAC".) I did similar things to liver cells in culture dishes, (which are easier to deal with, emotionally, but less like people). NAC did tend to save the lives of the poisoned mice and liver cells, and it is what I will recommend for you.

You might be wondering, if you want to boost glutathione, why not just eat glutathione? The problem with taking glutathione itself is that it gets broken down when you eat it, before it gets into your cells. Your body might put a portion of it back together, a little bit, after eating it, but eating it isn't the most efficient way to get it, ironically.

The best stuff on the market for increasing glutathione, that I know of from research, is called N-acetyl cysteine, also abbreviated as "NAC". It may also be called "L-NAC", which is exactly the same thing. The second best thing for increasing glutathione is L-cysteine, also called cysteine, but I would not recommend that since large doses can cause nerve damage. NAC is a slow-release form of L-cysteine and is safer.

Although I don't usually take supplements ( I prefer to just eat lots of nice-tasting herbs in my food!), I have taken NAC on occasion, perhaps because I was made curious by my own research, but then I never knew if it was doing anything. At least I never had any side effects. Reasonable doses certainly can't hurt, unless you don't need it, in which case it hurts your wallet.

I'm also put off by the lack of regulation of the whole herb and supplement industry, so at the risk of saying this for the millionth time, I wouldn't take anything unless I checked out the product first with an independent lab that evaluates various supplement products, called Consumerlab. (You can find them at consumerlab.com. and search their database with a yearly subsciption fee which is fairly inexpensive, I think.)

Sadly, consumerlab has not yet evaluated NAC or other glutathione-boosting supplements just yet. However, NAC is fairly easy to synthesize and purify, although it does oxidize a bit over time. The oxidized version of it in the supplement is unlikely to hurt you, anyway (but less likely to work.) Unlike herbs, which are easily contaminated with pesticides and vary quite a bit in the concentrations of active ingredients, a bottle of NAC ought to be fairly pure. It also ought to be far less expensive than the product on that website you asked me evaluate.

At our local health food store, NAC should not be more than 10 bucks for a bottle of pills, I'm guessing. It was dirt cheap from the chemical companies our lab bought it from, too, so there is no reason for these supplement companies to inflate its cost.

I would definitely avoid any NAC combined with other ingredients, however. You don't know what those other ingredients may do.

Hi Holly,
My doctor tells me that licorice can make my high blood pressure worse. Is that really true? How does that work?

Licorice lover in L.A.

It might. The mechanism is complicated, but I think it's a fun one! (OK, I perversely enjoy complicated mechanisms.) And you can certainly understand it if you want to hang on and read below. For even greater detail, with published references, read my licorice chapter from Herbs Demystified.

The occasional licorice induced hypertensive crisis does occur, typically with already hypertensive folks sitting around eating gobs of licorice every day for weeks at a time having to be admitted to the emergency room. This sort of crisis isn't all that common, however.

That's because you have to consume a lot of licorice, and it has to be REAL licorice. Most of the licorice sold in the US has had its active, blood pressure-raising ingredient removed. If you look at a product label for US licorice, you will often see the term "de-glycerrhizinized licorice". This sort of licorice won't raise your blood pressure.

In fact, a lot of US "licorice" candy has no licorice in it at all, and is flavored with similar tasting anise! (Anise, and fennel, for that matter, do not have this active ingredient, although they all taste similar.)

Europeans have always preferred real licorice. I can find it in some European import stores in my neighborhood, and it is some pretty strong stuff! (For an added hypertensive kick, the imported, Scandinavian type of licorice has a ton of salt added to it! It's an acquired taste.)

Also, the demand for real licorice in the US is rising, and you can now find in health food stores marketed as "real" licorice candy. Certainly a lot of "herbal" teas which are not labeled "licorice" still use licorice as a sweetening ingredient. You would have no idea licorice is in it unless you looked at the list of ingredients.

I mention this since one case study involved a man who drank a several cups of a tea containing licorice every day for years before he went to the emergency room.

The active ingredient in licorice root is a steroid-like, sweet tasting molecule called glycerrhizin. (Yes, it looks like Welsh to me, too.)

Glycerrhizin overdose mimics a syndrome called "Apparent Mineralocorticoid Excess". This can result in a trip to the emergency room where a patient presents with a crisis resembling an excess of the hormone aldosterone. Aldosterone causes you to retain sodium and pee out potassium, and it raises your blood pressure.

Scientists used to think that licorice simply mimicked aldosterone, especially since it LOOKS like the steroid hormone aldosterone. That's a very reasonable conclusion, but it's wrong!

The mechanism is a bit complicated, but basically glycerrhizin turns off a class of enzymes called "short chain dehydrogenase reductases", or SDRs.

Interestingly, one effect of turning off these enzymes in you gut is that the gut makes more mucous and less acid (the SDRs would otherwise disable prostaglandins that do this trick) so it does seem likely that real licorice can help soothe an inflamed gut.

On the other hand, the glycerrhizin turns off the SDR enzyme that ordinarily keep cortisol from acting on the kidney. Since cortisol acts just like aldosterone, binding to aldosterone receptors on the kidney, and cortisol levels are a lot higher than aldosterone, normally, this causes the kidney to "think" that aldosterone is sky high. Cortisol in the guise of aldosterone causes potassium loss, sodium retention, and consequent water retention with hypertension.

From what I can tell of all the case studies I've read of licorice eaters going to the emergency room, it takes a LOT of licorice to do this trick. So the occasional moderate snack of real licorice probably isn't going to hurt.

So, if you do have high blood pressure, perhaps you should have de-glycerrhizinized licorice, rather than real licorice, or keep your consumption of real licorice down to reasonable levels.

First of all I'd like to say that I'm not a science student or any kind. But lately I came accross this Prostaglandin F2 alpha (PGF2a) thing.
I read it somewhere it said that elevated level of PGF2a causes Dysmenorrhea ?
Is it true AA [Arachidonic Acid (an omega-6 PUFA)] can be found in linoleic acid (LA)? But isn't AA can be found mainly in animal only (errmm..said wikipedia) and LA is abundant in vege oil like olive, sasame, etc?. So which is which? My home usually cook with red palm oil.
What sort of herbs stimulate or has PGF2a or has AA then (since AA is the precursor of PGF2a, yes/no?)?

Thanks!
Not-a-science-student.

Hi Not-a-science-student!
Well, for someone who “isn’t a science student”, you are asking a pretty sophisticated and important question.

You can get my book from a library or you might enjoy irritating Barnes and Noble by leisurely reading it in their lounge with a nice latte without committing to buy it. Then just look up the flax seed, evening primrose, and borage seed chapters, and you will see more than you probably ever wanted to know about how these fatty acids like linoleic acid and arachidonic acid get converted to different prostaglandins. But to save you from this, I took some excerpts from my book below, and added more to address your specific question:

I don’t like to tell people what they should and shouldn’t take (there are enough people out there doing that already!) but instead I like to look at the cause and effect molecular mechanisms by which a substance works. Some mechanisms are better for some people than for others.

Also, we can’t judge a substance based on where it is from—any more than we can judge a person based on where they are from—that isn’t helpful or informative. You judge them based on what they do, and how they do it! So regardless of whether it is from “nature” or a lab bench (I argue that people are animals and part of nature anyway so this distinction doesn’t mean much to me) I just look at the mechanism and ask, is this an appropriate mechanism for your individual body? It does seem, however, that I keep finding that it is better for us to get more of our food from plants than from animals. You at least seem to be trying to do this with your red palm oil--that's good!--but you could make some better choices for oils.

But let’s get some terms defined, first.

You wonder if a certain prostaglandin causes menstrual problems, and the short answer is, that particular prostaglandin you mention (PG F2-alpha) might. It is used as a medication to induce labor and causes uterine contractions, or what you might call “cramps” when you make it all by yourself to your dismay. And yes, the sources of that particular prostaglandin are omega-6 fatty acids such as linoleic acid. The most abundant omega-6 fatty acid in our diets is linoleic acid (LA), which our body can convert to arachidonic acid (AA) (another omega-6), and then that under certain circumstances can get converted to this particular prostaglandin (F2-alpha).

So, it isn’t true that “arachidonic acid is found in linoleic acid”—it is true that linoleic acid is readily converted to arachidonic acid in our bodies after our enzymes tack a couple of carbons onto the chain, lengthening it from 18 carbons to 20 carbons. So linoleic acid is a precursor to arachidonic acid. (Both are found in meats to some extent, when the livestock eats plant sources of them.)

Your red palm oil doesn’t have the glut of linoleic acid that other vegetable oils like corn oil, safflower, and sunflower oil have, but it does have about 10% from what I can see. It also has a lot of saturated oils, which are not essential, and these won’t oppose the conversion of linoleic acid into arachidonic acid, which is what you appear to be rightly concerned about.

If you want to oppose the action of linoleic acid metabolically speaking, you would be better off getting more omega-3 fatty acids from your oils. Flax oil, walnut oil, and fish oil (from fish or fish oil capsules) are excellent sources of these.

Although I’m not in the business of telling people what they should and shouldn’t take, there are times when I am compelled to shout out about what might obviously help a lot of people! Lots of nutritionists and health care professionals are concerned that we eat too much linoleic acid, which is an omega-6 fatty acid, and not enough of the omega-3 fatty acids. I used to be skeptical about this, when the topic was raised 20 years ago! But after reading lots of boring scientific research articles on fatty acid metabolism, I’ve been thoroughly won over by this argument, too.

I admit it; it’s really an oversimplification for me to classify all omega-6’s as “bad” and all omega-3’s as “good.” The problem is their ratio in our diets. If you look the assortment of fatty acids in the modern diet, the “rare” essential fatty acids are the omega-3’s, and this has some health experts worried. They argue that our diets once possessed a 1:1 ratio of omega-6 to omega-3 fatty acids that is now skewed in favor of omega-6’s as high as either 10:1 or 20:1, depending on which expert you talk to. Modern society has recently become so adept at harvesting and using certain vegetable oils—corn oil, safflower oil, soybean oil, and sunflower oil—and these are all loaded with the omega-6 fatty acid linoleic acid. This we to feed to our livestock in the form of corn, a source of omega-6 oil, rather than their preferred grass, enabling even our commercial meat supply to be unbalanced with omega-6’s. Grass-fed livestock has more omega-3’s. Omega-3’s are abundant in fish oils and flax seed oil, and present to a lesser extent in other vegetable oils and nut oils.

So what’s wrong with eating linoleic acid? You do need some linoleic acid because you can’t make it. This puts it in the class of “essential” fatty acids. Obviously it’s better to have essential fatty acids than the non-essential ones that we already make, like saturated fatty acids. These are the infamous artery-clogging agents found in animal fats. Possibly even more menacing are the relatively unnatural “trans” fats created by partially hydrogenating oils, that many fast and processed foods are now dripping with, and like saturated fats, these are also tied to health problems. On the one hand, people who have more essential fatty acids than non-essential ones generally fare better, health-wise.

On the other hand, some essential fatty acids are healthier than others. The proportion of linoleic acid in our diet is disproportionate compared to other essential fatty acids. A glut of one type of essential fatty acid drowns out the beneficial actions of the others.

This is where people start talking about those omega-3 fatty acids and omega-6 fatty acids, which we have to get in our diet, because we can’t make them, and so they are called “essential”. These have some obvious fates after we eat them. Either they get “burned” into carbon dioxide for energy, or we will merrily stash them away as fat, regardless of our opinion about that, and they also get readily incorporated into the material making up our cell membranes—the outer boundary of our cells. Indeed, you can see what sort of fatty acids someone has been eating by looking at whether their cell membranes contain omega-3 derived fatty acids or omega-6 fatty acids—you really are what you eat.

The reason the terms 3 and 6 are used is because it matters whether an prostaglandin is made from one or the other. The “3” or the “6” indicates the position of something called a double bond in the fatty acid. The reason we care about that is that that position tends to stay in place as the fatty acid gets chemically changed in our bodies. So, an omega-3 will remain an omega-3 as it is transformed into other fatty acids, and an omega-6 will remain an omega-6 as it is transformed into other fatty acids. Thus the ratio of the kinds that your are eating will be preserved even after they are chemically altered into other fatty acids by your body.

The prostaglandins are part of a larger group of similar molecules collectively called eicosanoids. The “eicos” means 20, as they are all formed from fatty acids that are 20-carbons long.

Keep in mind that both omega-3s and omega-6s compete for the same enzymes to convert them to other more physiologically active molecules. So by eating more omega-3's, you can slow down and reduce the conversion of omega-6's into things like that prostaglandin you are worried about.

Eicosanoids, classified as prostaglandins, thromboxanes, and leukotrienes, work only briefly in tissues nearby where they are generated, and are thus called “local” hormones. Nonetheless they have powerful and often opposing actions on blood pressure, blood clotting, pain and inflammation, allergic and immune responses, uterine and gastrointestinal cramps, digestion, brain development and mood, even tumor development and growth...in other words, just about everything you can think of!

Both classes of essential fatty acids, the omega-3’s and the omega-6’s, are used to make 20 carbon fatty acids, which are transformed to hormone-like eicosanoids. The types of essential fatty acids you have stored influence what types of eicosanoids you tend to make. At the risk of oversimplification, I’ll come to the punch line: the omega-6 fatty acids generally make more pro-inflammatory, damaging eicosanoids. Eicosanoids derived from the omega-3 fatty acids are more anti-inflammatory and protective. Inflammation is just our protective systems gone overboard, so to speak, so the omega-6 system of eicosanoids isn't bad, it just seems that we are overdoing it with with the supply of omega-6 in the modern diet.

Alpha-linolenic acid, or ALA, is the main omega-3 fatty acid in flax seed oil, and you can readitly turn it into at least one valuable fatty acid found in fish oil. ALA gets incorporated into your cell membranes and fat after you eat it, so you store it. Ignoring minor pathways, it has two general fates: it can either be “burned” for energy, or turned into another omega-3 fatty acid. This is typical: omega-3 fatty acids, when metabolized by your enzymes, can only be turned into other fatty acids of the omega-3 class, and omega-6’s can only get turned into other fatty acids of the omega-6 class.

The 18-carbon ALA is lengthened by 2 carbons and 2 more double bonds are added, to make eicosapentaenoic acid, or EPA. This is one of the essential fatty acids in fish oil that everyone is now raving about for its health benefits. If you haven’t heard lately that nutritionist want you to eat more fish oil because of its omega-3 fatty acids, you’ve been living on another planet. If you don’t eat fish, you can make at least one fish fatty acid, EPA, by taking flaxseed oil. Why is EPA so exciting?

Medical professionals are rewriting the textbooks, literally. We are only now becoming aware of how important EPA derived eicosanoids are. In fact, if you look at even relatively recent medical textbooks, they only discuss ones derived from the omega-6 fatty acid, arachidonic acid, and barely mention the ones derived from EPA. Most texts are now being revised to include discussions of their activities, fortunately.

EPA derived eicosanoids perform the following healthy tasks. EPA is used to make the following menu of eicosanoids: prostaglandin E3 (PGE3), prostacyclin I3 (PGI3), thromboxane A3 (TXA3), and leukotriene B5 (LTB5).

Now here is what the omega-3 derived eicosanoids do. Hold on, this is a lot of data:

PGE3 has an anti-inflammatory mode of action similar to that of steroids like hydrocortisone: it prevents the omega-6 eicosanoid precursor arachidonic acid from being liberated from cell membranes, thus halting its conversion into inflammatory omega-6 derived eicosanoids. In addition, PGE3 reduces intraocular pressure, so scientists are now looking at it as a possible glaucoma treatment.

PGI3 is anti-inflammatory by the same mechanism: it prevents arachidonic acid release, plus it potently inhibits blood clot formation.

Similarly, the leukotrienes derived from omega-6 arachidonic acid are countered by the leukotrienes made by EPA. The leukotrienes made from arachidonic acid (such as LTB4) mediate the distressing bronchoconstriction in asthma, as well as chronic asthmatic hypersensitivity and acute asthma attacks. They are also involved in the inflammatory processes seen in disorders like cystic fibrosis, inflammatory bowel disease, and psoriasis. Although the leukotriene B5 derived from EPA also signals the immune system, it does so more weakly by an order of magnitude, and competes with formation of the more inflammatory leukotrienes. Thus it tames the immune system’s response, without shutting it down.

You can’t easily turn flax seed oil’s ALA into the second valuable fatty acid in fish oil, at least not very well. I write this to correct a common misconception still bandied about the nutritional literature. Fish oil’s other valuable omega-3 fatty acid is the 22-carbon long docosahexaenoic acid, or DHA. Although humans have enzymes capable of turning ALA into DHA, human studies repeatedly show that we just don’t do it very well, though some sources (often associated with flax oil sellers) glibly say that you can. This is frustrating, if you realize how important DHA is, and if you don’t eat fish oil!

Recent data suggest maybe this is because excess linoleic acid (the omega-6) opposes this conversion, so maybe you can convert ALA to DHA if you lower your linoleic acid intake enough. So that's potentially good news for the non-fish eaters out there, (and good news for fish) but I am waiting for more data to see that hypothesis can be better supported.

DHA is not used to make eicosanoids (it doesn’t have the prerequisite 20 carbon length chain for that) but it is of startling importance in the brain’s growth, development, and signaling, as well as retinal function. Because of the growing awareness of our requirement for DHA and our limitations in making it, some are now suggesting this fatty acid is essential on its own, because ALA isn’t a very good precursor to it. There are even interesting theories about how pre-hominids required moving from the trees to an environment next to water, to obtain a source of fish. This supposedly helped them to evolve better brains, but I am not an an anthropologist.

I am not sure what to recommend to strict vegetarians because of this, and I do sympathize (I’m a vegetarian, but I joke that I am now a bad one because of these studies I have read—I’m not a strict one, and I take fish oil. And OK, I like to eat fish!) It’s possible you can make some DHA from flax seed oil, but don’t expect to make a lot. The fish oil has omega-3s simply because certain fish eat certain cold water algae, which supply the fatty acids themselves. So maybe we can just grind up some vat grown algae in a blender and mold it into the shape of a fish and not hurt the ocean's ecology. I'll eat it, I'm easy.

I may have gone a bit off topic there, but there is so much to say about these interesting essential fatty acids! Somebody shut me up! So try getting more omega-3 oils from one source or another, and limiting your linoleic acid intake. I hope that helps!

Hi Holly,
I came across your site today and filled with awe of how much you know. Therefore I would like to ask your for your insight concerning an issue, most people I came across on the internet, are silently suffering from.

I am aware of apocrine glands in the armpit and ano-genital area. I do know that when one sweats in these regions, if it mixes with bacteria, it would give off offensive odors. What I don't understand is that, even though when some people wash off the sweat, and apply deoderant and antiperspirants, there still seems to be offensive odor given off.

I have also noticed that after taking a shower, maybe 5 minutes of more, I might start to give off odor from the armpit. I have tried various remedies I came across online, to no avail. I currently use an antiseptic soap and dove, but the issue persists. This is really affecting me psychosocially, physically and so on. I always dreaded going to class because I noticed some of my classmates could perceive the odor(by their body languages).

I came across a site called drnatura.com, have you heard about it and what do you think about one cleansing out oneself? They say that it is good for one to periodically cleanse out the GI system, and toxins from the other systems in the body. I am thinking about giving it a try, to see if it rids me of this odor. By the way the odor recently started towards the end of spring '06. I don't sweat excessively (no hyperhidrosis), its the odor i'm concerned about.

I also recently noticed/feel some excessive heat inside me (whole body). Its quite uncomfortable, but when my temperature is obtained, it is usually within normal limits. My labworks seem to be normal i.e. thyroid studies, liver functionand so on. I went to see my doctor regarding the armpit odor issue,and asked for a refferal to a dermatologist. The doctor simply disregarded my request, and informed me that she'd consult the dermatologis herself. I received a note from the doctor to limit fat/salt/cholesterol intake, which I don't often consume.

There are numerous people whom I came across that suffer from this issue. I truly would appreciate it if you could give me some advice.
thanks

Well, thanks for the praise, but I don't know everything. That is why I have to constantly look up stuff all the time and re-evaluate what I think I know! I recommend some of the sites on "relatively reputable resources", in the margin of my website, here.

I am sorry to say it, but as appealing as the idea of cleansing your GI tract may sound, an unclean gastrointestinal tract is not your problem. "Cleansing your GI" will not help you one bit, it will just clean out your wallet. It is a popular fad based on a medieval notion that some sort of undefined "toxins" (they never give them actual chemical names so I can look them up!) in the body are causing problems, and need to be cleansed with attacks from above and below with laxatives and enemas, or other devices. The idea has not a bit of sound scientific evidence to support it, although it is an easy thing to picture, especially for medieval minds.

To read more about GI cleansing, take a look at Dr. Stephen Barrett's article. (I especially like the protest from a colon cleansing enthusiast that he politely adds at the bottom of his article, pretty much handing the poor person a rope that they then gleefully hang themselves with. It is filled with grammatical errors, conspiracy claims, and the eyebrow-raising claim that our intestine has a BRAIN! I must have missed that one in my anatomy class.)

The good news is that I really think a dermatologist can help you. I know you say you don't have problems with excessive sweating, but you might want to check out possible treatment with botox injections, which can control sweating. I'm not sure what the verdict is on using that for odor, but I understand it is a life saver for some who have excessive sweating. If your dermatologist doesn't help, see a different one. Of course, we will assume you are bathing every day!

I'd also recommend seeing an endocrinologist. I am not sure what you mean by "excessive heat" in your body. You have not revealed your age or if you are female, so that may make sense if you are entering menopause, which can happen prematurely for some women. Whether you are female or not, an endocrinologist will be better than your average MD at sorting out any hormonal imbalances that may cause a sensation of heat or overactive apocrine glands. If you have a fishy smell, you may have a relatively rare genetic condition that you should get checked out by an MD.

I hope that helps you get started on the right path! Now make peace with your colon!

You describe very clearly how antioxidants protect our cells, and in your book you also describe which plants have interesting antioxidants and how they work, but when it comes to people taking antioxidant pills, you become suddenly skeptical to the idea. How do you reconcile these points of view? -Lucas

Hi Lucas,

The bottom line is this: I still am excited about antioxidants, don't get me wrong. But antioxidants in pill or supplement form don't do anything dramatic according to the best clinical studies. Not only are some very expensive, but large doses of them turn them into free radicals and oxidizing agents, the very thing you are trying to avoid, by taking them.

First, you need to know that oxidizing agents and free radicals (which are often the same), generally known as ROS (reactive oxygen species) are an unavoidable consequence of cellular respiration--and these ROS do damage to our cells. It There is good evidence that these ROS may initiate many of our common diseases and general aging. Antioxidants (which chemists call reducing agents) neutralize ROS by a variety of mechanisms.

People who eat a lot of fruits and vegetables are less prone to diseases--the very diseases that we think may be caused by oxidizing agents. Now, people have formed a logical theory that since plants contain many antioxidants, these antioxidants are combating ROS and their associated ill effects. But hold on to your hats--this is just a theory and it may be all wrong!

We actually don't really know why people who eat a lot of fruits and vegetables live healthier lives. Perhaps the many studies are "confounded"--that is, what else do people who eat lots of fruits and vegetables do? Probably exercise, buckle their seat belts, avoid smoking, and all that. We try our best to statistically weed out confounding factors in these observational studies, but if you are a good scientist, you have to be honest and admit that some confounding might be going on.

Just because you can imagine a great mechanism, and see it take place in a test tube with isolated cells, does not mean that same mechanism will work in a person.

Well, here we were with this lovely theoretical mechanism for how antioxidants from plants could be helping us live longer lives. So based on this theory, isolated antioxidants in pill form ought to be great, right?

Wrong! We all held our breath for years as study after study came out, testing everything from classic antioxidants like vitamins E and C, to more obscure polyphenols and glutathione and so on. Nothing that dramatic appeared. For the most part, the only time you saw a noticeable effect is when the lab animals or people started out with a deficiency in the item tested to begin with. In some cases large doses of antioxidants proved harmful--one of the most dramatic cases was with beta carotene significantly increasing cancer among smokers, to the point that the investigators had to pull the plug on the study to save the participants. Large doses of tannins may cause cancer. Large doses of quercetin make you dizzy and make you throw up, and can cause tingly nerves in the extremities.

As someone who has synthesized and tested antioxidants in the lab, and been in on some of this research, I can't tell you how disappointing this has been for me.

But nature is always trying to tell us the truth through the data, I believe, and you always have to look especially hard at data that you don't like, because it might be telling you something even more wonderful than your previous conceptions allowed. Nobody likes to toss out their pet theories. But science forces us to do this repeatedly. I really trust that the truth is in good data, even data we don't personally like.

So for now it seems like a good idea to just eat your fruits and vegetables,drink tea and/or coffee (with or without caffeine) and put your favorite cooking spices and herbs on your food to flavor it. I would definitely skip the supplements.

Now, why might antioxidant pills be so ho hum in clinical studies? There are lots of good theories:

1) Targeting to mitochondria

One of the most intriguing theories, to me, is that antioxidants don't work unless they get to the very place where they are most useful--the mitochondrion. This is the cellular structure where respiration takes place. It is where about 90 percent of our oxygen gets used. This is the place where most of the harmful ROS are generated. Even cells in culture with antioxidants dumped on them may absorb the antioxidants, but the antioxidant still doesn't get inside the mitochondria in the cells.

Recently, chemists have synthesized antioxidants that are targeted to mitochondria. That is, they have given them chemical mailing addresses, so to speak, that help deliver them to the mitochondrion. (Actually, this is just a consequence of electrostatic forces--the inside of a mitochondrion is mostly negatively charged, and they put permanent positive charges on these antioxidants, and since negative attracts positive, the force of the charge pulls the drug into the mitochondrion.) So far no people, to my knowledge, have taken these mitochondrially targeted antioxidants, but they are getting positive results in studies with cells and rats.

2) Absorption into the bloodstream

Antioxidants in the polyphenol class in particular, including flavonoids, are notoriously bad at making a one way trip through your digestive tract, down to the bitter end. Many are physically large, and bind to proteins in your gut in some cases, literally "tanning your hide" in your gut in the case of tannins. Resveratrol in grapes is SO exciting--in test tubes. But just try to get that sucker into your bloodstream. OK, some trace amounts can get through, but those then are swiftly metabolized into other things. It may still be that their action in the gut alone is not to be dismissed and is helpful. Some scientists have proposed that in plant foods, the fiber of the food slows the release of such polyphenols so they are absorbed more efficiently, as opposed to in pill form. That is a good theory, but remains to be tested.

3) We actually need oxidizing agents and free radicals.

I have had to laugh out loud at some supplement sellers, who paint all free radicals as bad, if not actually "evil"! One described free radicals as "having only one purpose, to destroy you"! (Just a note--chemicals are not alive and have no purpose, and can't really be regarded as good or evil).

It would have indeed raised the eyebrows of the writer of this alarming passage to learn that many free radical scavengers work by becoming stable free radicals. So, these stable free radicals are actually helpful. Also, we need free radicals in the right places--we need a smattering of nitric oxide in our blood vessels, which is a free radical and a simple gas, as a very important hormone like molecule that lowers our blood pressure and performs so many other important functions.

So it is not that free radicals and ROS are "bad" and antioxidants are "good", but we need both, in the right places, and in balance with each other.

4) Plants also contain ROS. Maybe these are helpful.

Plants make all sorts of toxic things, often functioning as insecticides and antimicrobials (since they can't run away from insects and pests, they tend to synthesize some nasty chemical weapons). That is one reason why, as a chemist, I find plants so fascinating--they are much better synthetic chemists than I could ever hope to be. Not only does coffee and and tea--my own favorite plant derived products--contain a lot of antioxidants, but they also contain ROS like hydrogen peroxide! One theory is that these ROS kick-start our defensive processes like the induction of the synthesis of new antioxidant enzymes.

The bottom line is that the story is never as simple as the supplement sellers would have you believe--but it is far more interesting!

could rooibos help lupus pains like yerba mate did ?
is rooibos in your book ?
in 7 years of yerba mate in the morning i never even needed 1 aspirin .
10 days without yerba mate the pain is draining me away.

i am so grateful to ask you this right now.

Hi Lucy!
I am so sorry you have lupus. I don't know why you find that yerba mate helps it, I have not seen any studies on that. They have not been done.

Perhaps antioxidants from the tea have an antiinflammatory effect? I don't know! That is just a wild guess on my part.

The only concern about yerba mate, is that there is some association of people who drink it for a long time, and esophogeal and digestive tract cancers. This is controversial, but it is something to certainly consider. Do keep getting regular check ups and tell the Dr. about that possibility of a link to cancer, so they can make sure you are OK in the that regard.

The caffeine that is in yerba mate is not a problem, despite what people may tell you. If you feel awful when withdrawing from yerba mate it may very well be caffeine withdrawal, which can feel very bad. Despite the problems with withrawal, regular, moderate caffeine intake is actually associated with several health benefits. Other caffienated drinks that also have a good dose of antioxidants are regular green or brown tea, and coffee. They might make you feel better, too.

I wish I had rooibos in my book, but I ran out of time before my publishing deadline! In the next edition I want to include more herbs, including rooibos or "red bush tea", since it has become so popular. But there are hardly any good scientific studies on it. The good news is that rooibos is not known to have any obvious negative effects, so you should have as much as you like. It has no caffeine, and since it is not made with the tea plant (Camellia sinensis) it is considered "herbal" tea. Rooibos does contain some good antioxidants.

For lupus, there is some evidence that taking flaxseeds might help, and also vegetables in the broccoli family: broccoli, cabbage, and brussel sprouts, that is. Both contain agents (lignans in flaxseeds and indole-3-carbinol in the cruciferous vegetables) that switch estrogen into a less active form of estrogen, and estrogen is thought to play a role in the symptoms of lupus. So some researchers theorize that flaxseeds and cruciferous vegetables in the diet might help people with lupus.

You say that Arnica should not be taken internally but I was recommended
by my doctor to take it in pill form before having rhinoplasty. I got
the 6c strength and have to take 5 twice a day.

Thanks!

Hi Alisa!

Indeed, while many herbs are safe, arnica is not one of them. People taking it internally have died. But what you are taking does not contain any arnica, because the "c" indicates it is a homeopathic remedy. So at least it won't hurt you.

Homeopaths believe that you can dilute an herb to the point of nonexistence in their preparations. They believe the water contains the "memory" of what was once in it. This is an 18th century mystical belief that has never been proven by any scientific study, although scientists have tried to proove it and failed repeatedly. One French study published in Nature, where even the editors took the unusual precaution of saying they did not believe it but wanted people to try to at least duplicate the experiment, suggested that something might be going on, but the researchers were later found to have thrown out all the evidence that did not support their theory--they just said it was "bad data", although there was nothing really wrong with it. In science, you aren't allowed to throw out data that doesn't agree with your pet conclusion. That is called "data selection", and if you do it knowingly, it is a type of fraud.

Nonetheless, a lot of people still cite this work as evidence for homeopathy.

You would have to drink a volume of the solution as large as the planet Earth to get one molecule of arnica, so you don't have to worry about any arnica in your preparation. For this reason, I don't personally recommend homeopathic remedies, even though they are very popular.

I recently just found out I am pregnant with my second child. When I went to my OB/GYN today he told me to no longer use cocoa butter. The reason being that it contains caffiene and it has been known to cause irregular heartbeats in fetus' and infants.

Women have been using cocoa butter for centuries and I don't know what the difference is now.

Can you find out if this is being told to others and if I should stop using the product.

Thank you

LR

Dear LR,

Keep enjoying your cocoa butter. It sounds like your doctor means well but is misinformed. I can relate; at the risk of losing your confidence I will confess that I am constantly making flight corrections in my thinking, because what we learn from new studies always forces us to look at the data anew! Nature shows us the data, and we have to keep our minds open in order to see what she is trying to tell us.

I have some research articles below that your doctor can read to clarify the points that I make here, if they are open to such a thing.

First, cocoa butter contains no caffeine.

So relax and enjoy your cocoa butter. If it is not processed completely it might contain teensy weensy iddy bitty little traces of caffeine that are entirely negligible in concentration; and these would be too scant in concentration to affect you physiologically, unless you spent all day eating multiple vats of cocoa butter.

Cocoa butter is mostly saturated fat, but does not seem to be associated with increasing cholesterol or with increasing bad (LDL) cholesterol, from what we can tell, so far. Of course, any fat is highly caloric, and cocoa butter is no exception. Most of us should cut down on our total calorie intake, so if you eat a lot of "good fats" from plants, cut down on calories from other sources. A little bit of fat can't hurt if it is "good fat". Cocoa butter doesn't seem like a bad fat to have. And we all need some "good fat" triglycerides in our diet.

Of course, if you apply cocoa butter to your skin, it makes a great moisturizing agent (as most triglycerides will!) and it would be utterly absurd to think that any negligible, trace amounts of caffeine could be capable of penetrating your skin to become systemic.

Second, it isn’t at all clear whether caffeine is bad for pregnant women, but a few observational studies show that only a fraction of women drinking more than 3 cups of coffee daily (in other words, an obviously jittery amount of caffeine) might have a problem. So pregnant women should cut back on their caffeine consumption. I have never seen any study suggests that they should avoid caffeine completely.

This is the only precaution concerning caffeine that has really caught my attention, other than the obvious milder side effects like insomnia, nervousness, and an inordinately frequent longings to pee, assuming too much caffeine is consumed.

This precaution does not surprise me, since too much of anything is usually bad for you. This is the first rule you learn in toxicology. You can die from drinking too much water, but it is really hard to do, for example.

When taken in moderate amounts, caffeine is associated with health benefits: decreased risk of Parkinson’s disease, decreased risk of suicide, and fewer gall bladder problems. Plus, the drinks in which caffeine occurs (coffee, tea, and chocolate) also contain significant doses of antioxidant polyphenols and flavonoids, which can be obtained in decaffeinated versions of tea and coffee if you don’t care for how caffeine makes you feel.

Earlier studies with caffeine were "confounded"; that is, researchers made the mistake of not worrying about other variables in an observational study. This is a potential problem with any sort of observational study, but it can be statistically controlled for if the researchers are prudent enough to worry about doing so. For example, former studies included people who both smoked and consumed caffeine, and the effects of smoking, which we know are bad, were not statistically edited out, so to speak, so the data was misleading.

Other studies involving animals can be suspect if tons of caffeine or any substance, indeed is used, because we know that the more you expose any animal to any particular substance, the more likely that substance will do harm. So you have to look at the doses in those studies and be more cautious about concluding a harmful effect, unless relatively small doses were used. For example, those famous studies of saccharin showing bladder cancer in rats used ridiculous megadoses of saccharin that no human would realistically take. (So I keep all my saccarin on the top shelf of my kitchen--where the rats can't get it.)

Cocoa beans are processed to provide two main products:

cocoa solids, also called cocoa liquor (although it has no alcohol). This is what we use as cocoa powder. This part has all the flavor of chocolate and contains caffeine. However, cocoa solids contain much less caffeine than coffee.

cocoa butter, which is the fat obtained from the bean. It is almost entirely triglycerides (what people call “fat”). Caffeine is not a triglyceride; it is in a different chemical class called a methylxanthine. There is no caffeine in cocoa butter. White chocolate, which is made from cocoa butter without the dark cocoa solids, therefore contains no caffeine, either.

The American public consumes a wide array of caffeinated products as coffee, tea, chocolate, cola beverages, and caffeine-containing medication. Therefore, it seems of value to inform both the scientific community and the consumer about the potential effects of excessive caffeine consumption, particularly by pregnant women. The results of this literature review suggest that heavy caffeine use (> or = 300 mg per day) during pregnancy is associated with small reductions in infant birth weight that may be especially detrimental to premature or low-birth-weight infants. Some researchers also document an increased risk of spontaneous abortion associated with caffeine consumption prior to and during pregnancy. However, overwhelming evidence indicates that caffeine is not a human teratogen, and that caffeine appears to have no effect on preterm labor and delivery. More research is needed before unambiguous statements about the effects of caffeine on pregnancy outcome variables can be made.

I am sitting here with your book, borrowed from the Aiken Public Library in South Carolina, and I am delighted! For years, I wondered why no one wrote something like that. I found your website, read your bio, and all I can say is thanks again.

I taught high school for almost 30 years, and always hoped I could inspire even a few of my students to do good work. I'm sure you inspire hundreds.

I have one question: why do I love the smell and taste of rosemary so much? In the 70's, in Pennsylvania, I started a vegetable garden out back and didn't even know what rosemary was when I planted it. But I always felt it must have something special to it.

Again, thanks, for a great book!

Dennis

Hi Dennis,

Did you know that rosemary can get into your brain after you smell it?

But first let me say that your message meant a lot to me, especially since you have also been a teacher, so you must know how challenging it can be to communicate ideas. Thank you so much!

This is the first book that I have written, so I had no idea what to expect. Already it seems to be gaining more notice than I would have expected, and I am deeply grateful. And thanks for supporting your local library--our libraries are so often forgotten but always in need.

About your affection for rosemary, who can say why it makes your brain so happy? Do you have a childhood association with the herb? Sometimes our brains link a particular fragrance to a vivid memory, and the smell always evokes that particular memory. I can't smell roses without thinking of my grandmother, who used rose oil liberally.

I can relate: You may have an affection for rosemary, but I know I get more happy than I have any right to get, every time I smell fresh basil. Perhaps this is because every time I bring basil into our kitchen, it signals a time of celebration, since my fiance and I have transformed pesto making into a household ritual signaling celebration.

In researching some of the nicer smelling herbs, like lavender and lemon balm, I was intrigued to learn that some of the small fragrant molecules, called monoterpenes, can get into your brain after you inhale them!

The reason that this impressed me is because this is not an easy thing to do for your average molecule. If you ingest molecules, most can not penetrate your "blood brain barrier", a barrier that chemically isolates the brain and spinal cord. This barrier is for the best, really, since you don't want any old foreign molecule potentially messing with your precious brain.

But many of those small, smelly monoterpenes from plant essential oils can penetrate the blood brain barrier, which is better at preventing water-soluble molecules from penetrating it than small oily ones. Some of the monoterpenes from lemon balm enhance the action of GABA (gamma-aminobutyric acid) in the brain, which slows your brain down. So the aromatherapists could be on to something.

"Rosemary for remembrance", Shakespeare wrote in Hamlet, but now we might add, "Rosemary for cerebral blood flow". The monoterpenes from rosemary include cineole, borneol, camphor, and pinenes, which give it its pungent, piney smell. One study using brain magnetic resonance imaging show that after people inhale cineole, cerebral blood flow increases. Rats sniffing borneol had increased hypothalamic levels of serotonin and histamine. Histamine plays a major role in wakefulness in the brain. (That's why certain antihistamines make you sleepy.) So the common subjective perception of rosemary as "stimulating" could have a biochemical basis after all.

Lastly, I can't resist mentioning one of my favorite and more amusing myths concerning rosemary. If rosemary thrives in a woman's garden, that woman supposedly dominates in caring over the household. I have to confess I'm secretly pleased that my own indoor rosemary thrives, and when I mention this to my fiance, he smoothly asks for the location of this offending herb so that he might do something about the situation. I tell him I forget where it is.

I was recently delighted to hear from an editor who works for Martha Stewart Living. She was writing an article on using the herb calendula as a topical treatment.

Not having any celestial source of knowledge, I did my usual thing and dug into all the published peer reviewed articles that I could find on the topic. I found the herb quite interesting, and am inspired to write an article of my own. Here are some of the tidbits that I learned and shared with this editor:

Botany and Culinary:

Calendula is related to marigold, and sometimes called “pot marigold”, but the marigold that most people plant in their gardens is not calendula. It is related to it; in the same family (Asteraceae, also called Compositae) but not the same genus (the genus of the marigold is Tagetes and that of calendula is Calendula).

Calendula grows very easily and has bright yellow or orange daisy-like flowers. (I once had some completely invade my garden here in Utah, it took me a day to pull them all out of my garden.)

Laying chickens are sometimes fed calendula flower petals along with their feed, which turns the yolks a brighter yellow from the carotenoid pigments in the flowers.

Some researchers are investigating the use of calendula extracts to kill snails that carry parasites in developing countries.

Safety: Although calendula seems generally pretty safe, there is insufficient information to recommend taking large amounts of it orally on a regular basis. A few petals here and there in salads on occasion, for example, is unlikely to hurt you. Pregnant or lactating women should avoid consuming it therapeutically simply because it is an unknown. It is in a family of plants that always raises a red flag for allergies. People with allergies to other plants in this family (ragweed, daisies, dandelion, sunflower, chrysanthemums, arnica, and other daisy-shaped flowers) are more likely to have an allergy to calendula, or to eventually develop one. People in this category should perform a patch test if they want to try calendula topically, and should avoid eating it.

Nonetheless, reports of allergies to calendula are uncommon in the scientific literature, compared to allergies of other asteraceae plants. There is one published report, from Russia, of a woman who gargled with a preparation of calendula and she suffered anaphylaxis, a severe allergic reaction:

Klin Med (Mosk). 1974 Apr;52(4):142-3.

Title: [Anaphylactic shock after gargling with an infusion of Calendula]

[Article in Russian]

Gol'dman II.

Publication Types:

Case Reports

Another study showed that after 433 patients were patch tested for calendula allergy, 9 responded positively, showing they had the potential for a bad reaction to calendula:

Department of Dermatology and Venereology, University of Innsbruck, Austria.

Animal tests show calendula is relatively nontoxic. Cell and animal studies show nothing alarming, but more studies should be done. Because studies are incomplete, a 2001 report prudently says “it is concluded that the available data are insufficient to support the safety of these ingredients in cosmetic formulations.” (This is not surprising since it is the status of all but the most thoroughly studied herbs.) At that time is was judged to be used in around 200 different cosmetic products.

Title:Final report on the safety assessment of Calendula officinalis extract and Calendula officinalis.

Int J Toxicol. 2001;20 Suppl 2:13-20. Review.

Homeopathic calendula:Homeopathic preparations of calendula (not to be confused with naturopathic or holistic) involve a particular method of diluting the herb down to nonexistence in the preparation. Homeopaths believe the preparation retains a “memory” of what was once it, which is really rather bizarre when you think about it. This has never been proven by any experiment, though people have repeatedly tried to prove it. There is no evidence that homeopathic remedies in general work any better than a placebo, although they have been repeatedly tested. (They can work by the placebo effect, which sometimes is impressive however.) Nonetheless, for this reason, I would never use or recommend a homeopathic preparation—I would prefer one that has actual calendula in it.

Formulation: Most of the folkloric and scientific use of calendula involves the use of the outer ray flowers. Each flower has many tiny “disk” flowers, as well, in the center of the flower, but these are not usually used, nor is the green part of the herb. Curiously, we now know that the ray flowers have the highest percentage of faradiol (farrah DIE-all) esters, which are thought to be antiinflammatory, and that could explain how they help skin to heal. (The faradiol esters were 10 percent higher in ray flowers than disk flowers, and 100 percent higher than the green bits.)

Also, the faradiol esters are oil-soluble, and not water or alcohol soluble. So the best method of obtaining them is to soak the outer flowers in something oily like vegetable oil, or petroleum jelly.

Faradiol esters are also found in sunflower petals, arnica petals, coltsfoot flowers, and dandelion herb. Arnica, however, often causes a rash, and the other plants are less well known.

The oil-based preparations will end up being colored, since carotenoid pigments that are colored are oil-soluble and will leach out from the flower petals into the oil. Carotenoids in moderate doses are known to be antioxidant and protective. (Megadoses of oral carotenoids may be harmful, though. Most megadoses of antioxidants end up being more harmful than helpful, unfortunately. I can talk about why that is, if you like, on your radio show...)

Water or alcohol preparations are less likely to contain the above faradiol esters and carotenoids, but more likely to contain common plant flavonoids, which are not unique to calendula but found in most plants. Flavonoids often act as protective antioxidants by a variety of different mechanisms, and may in theory have anti-cancer activity.

Faradiol esters’ activity: Faradiol esters in an a category of common plant molecules known as triterpenes (try-TERP-enes). Faradiol esters are “antiedemic” (relieve localized swelling of tissues) and antiinflammatory in a small number of animal studies. It is possible that other triterpenes in calendula have similar, but perhaps less potent, activities. Antiinflammatories in general relieve “heat, pain, redness and swelling”—the four common signs of acute (short term) inflammation. They can also speed healing. Inflammation is caused by the immune system over-reacting and causing damage. It is a case of friendly fire. Inflammation also commonly underlies, and we now think, perpetuates many disease processes. So it often helps to shut it off.

This study singled out the faradiol esters as the most active antiinflammatory agents in calendula flowers:

Planta Med. 1994 Dec;60(6):516-20. Title: The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers.

In the following study the faradiol esters from calendula were found effective in reducing the swelling of mouse ears that were treated with an irritant. A compound derived from calendula’s faradiol esters, called faradiol, was just as effective as indomethacin, a prescription antiinflammatory medicine which is similar to ibuprofen. J Ethnopharmacol. 1997 Jul;57(2):139-44.

Title: Anti-oedematous activities of the main triterpendiol esters of marigold (Calendula officinalis L.).

Institute for Botany and Food Science, University of Veterinary Medicine Vienna, Wien, Austria.

Freeze-dried calendula extracts protected mice from the inflammatory effects of injections of carageenan and prostaglandin E1 in another study. White blood cells normally infiltrate the site of injection, causing swelling, but calendula prevented this from happening.

How does it work? This is always what I am most interested in, because some mechanisms are better than others, some are safer than others. So far, we don’t really know calendula works, because those studies have not been done.

But there is a hint that water and alcoholic extracts of calendula do not work like aspirin and other related (NSAID) drugs. These drugs prevent an enzyme (cyclooxygenase or “COX”) from making prostaglandins, and some prostaglandins are known to promote inflammation. Calendula and a number of other herbs were tested for this aspirin like-activity (tested for COX inhibition). Calendula was not singled out in the article for COX inhibition as other herbs were, so it doesn’t seem to work that way. However this study used alcohol and water extracts and these extracts do not contain the faradiol esters, so they don’t say anything about how the faradiol esters might work. It might still be that faradiol esters act like aspirin (but their structure is not very aspirin-like so I personally doubt that.)

National Institute of Research-Developmentfor Microbiology and Immunology Cantacuzino, Bucharest, Romania.

Looking at the structure of faradiol esters, they look very steroid-y to me, that is, they look like steroids. Steriods can be either hormonal, or inflammatory, in general. Some steroids have activities both of hormones and anti-inflammatories. We don’t know if calendula has any hormonal activity, those studies have not been done.

One of the most well-known steroidal antiinflammatories is hydrocortisone cream, or cortisol. In theory, faradiol esters might act like hydrocortisone, because they resemble hydrocortisone, but that is not known, the studies have not been done. Hydrocortisone and other antiinflammatory steroids work by preventing the precursor to prostaglandins (called arachidonic acid) from getting released from cell membranes. Aspirin-like drugs, on the other hand, prevent this arachidonic acid from being turned into prostaglandins by the enzyme cyclooxygenase (“COX”).

Clinical studies with actual people: These are always so much nicer, for so many reasons, than animal studies. There is only one well-designed one. This is a French study comparing oil-based calendula extracts to trolamine, published in the Journal of Clinical Oncology.

The punchline is that women using calendula (126 women) had statistically significantly less acute dermatitis than those using (128 women) trolamine (trade name Biafine). The dermatitis that radiation therapy causes is similar to sunburn, but can be more severe, with red skin, peeling, and blisters forming. The women using calendula also had less pain and this effect was also statistically significant. What I thought exciting about the study was that the women using calendula were more likely to continue radiation therapy without interruption, which is more likely to get rid of their cancer.Patients in the trolamine group requested 12 total suspensions of radiotherapy treatments because of dermatitis, but only 1 patient in the calendula group requested an interruption in her therapy, and that request was not related to her dermatitis.

J Clin Oncol. 2004 Apr 15;22(8):1447-53.

Title: Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.

You can read the article yourself if you want, if you link to http://www.jco.org/cgi/reprint/22/8/1447

The authors of the study are up front, which is nice, about a couple of limitations of their study. First, they did not compare calendula to an inactive placebo, which would be more ideal so we could see just how effective calendula is. But it perhaps it would have not been kind to give half of the women an ineffective skin treatment after their breasts were burned with radiation. Trolamine is often used on skin after it has been treated with lasers or radiation therapy. It actually is not thought to be all that effective, so in that respect it may have acted somewhat like a placebo.

Another limitation of their study was that it was single blind, not double blind. Ideally, you want neither the subjects nor the scientists to see who is getting what, so no one can subjectively form any preconceived bias for a particular treatment. But the calendula ointment is yellow, so it was impossible to disguise it from the patients. So they knew what treatment they were getting. The doctors, on the other hand, did not know who got what treatment, since the patients could were required apply their ointments many hours before their skin was examined by the doctors, and by that time their skin was not yellow.

The article mentions several times, by the way, that 30% of the women using calendula did not like applying it, (compared to 5% of the women using trolamine.) The article didn’t say why. Perhaps they did not like putting something so yellow on their skin, or perhaps the tactile sensation of the ointment was unpleasant. Trolamine did not have such a problem with compliance.

Rare and previously undiscovered carotenoids in calendula flowers: Carotenoids are a type of plant pigment that is common in plants; they are often yellow, orange, or red. They are likely anti-oxidant and free radical scavenging (that’s a good thing.) I was intrigued that three new versions of lycopene were discovered in orange, but not yellow, calendula flowers. The common form of lycopene, that we are most familiar with, is what makes tomatoes red. (These new versions have similar structure as chain-like molecules, but are “cis-trans isomers”, that is, they bend in different ways along the chain at locations of double bonds.) Orange calendula flowers also contain some carotenoids that are relatively rare in nature. We don’t know what their properties are, if any, but it is likely that they are at least similar in activity to other more common carotenoids:

I have a skin question. I read recently that alpha hydroxy acids will not work if they are in a "pH balanced" formulation. Is this true? If so, how can I tell if I am spending a lot of money for a product that won't work? Can I change their pH and make them effective?

PG.

Dear PG,

What you read is true. Alpha hydroxy acids will not be in an active (acidic) form if they are "pH balanced", or in other words, neutral, at pH 7. Some of these products are quite expensive, and I was surprised to learn that a portion of even the expensive products do have a pH which renders their effectiveness questionable.

The reason I took a while to answer your question is because I wanted to buy a number of products and test them. At work I can use a pH meter, but in my kitchen I use simple litmus paper which is readily available off the Internet to buy, and it ought to be dirt cheap. I buy mine from a local beer making supply store, and normally use it in testing wine that I make. You can get your own litmus paper and test your sample, so you can do the same. I'd get a couple of types for ranges of values below 7 if you are testing your products.

If the opacity of the formulation is a problem, try diluting the material 1:10 in water, preferably freshly opened distilled water. (Carbon dioxide from the atmosphere dissolves into standing water and normally makes water a wee bit acidic.) The alpha hydroxy acids are water soluble and will leach out into the water. Then, the pH that you measure will be higher (more basic) than the true value by one unit, (since pH is a log scale and you diluted by ten.) So if you do dilute the material tenfold, subtract 1 from the pH that you measure. This should get you a crude estimation of the pH.

But what pH do you want?

In order for half of the alpha hydroxy acid present to be in the active, acidic form, the pH of the solution must be equal to something called the pKa of the acid. Acids have different pKa values, it is a measure of how strong they are (the lower the number the stronger they are.) If any of my three readers out there (excluding my mom) are dying to know more about pKa values you can read my review of acid base chemistry. Here are some common alpha hydroxy acids and their pka values. You can see most are around 3.

glycolic acid 3.74

lactic acid 3.08

malic acid 3.40

tartaric acid (meso form) 3.22

alpha-tartaric acid 2.98

citric acid (has three acidic regions on it, and all three have different pka values: 5.19, 4.77, and 3.15.

You could always lower the pH of your formulation and make it more acidic. Acidic solutions, by definition, contain an excess of hydrogen (H+) ions. So why not buy a bottle of hydrogen ions and add them? Well, you can't! That is because a bottle of hydrogen ions doesn't exist. Ions of like charge repel each other. The next best thing to do is add something that is not charged, which can release hydrogen ions.

An acid is something that can release hydrogen ions (or split water in two and hold onto one half of water and release the rest as a hydrogen ion.) You can always make your formulation more acidic by adding some mild acid, like a few drops of vinegar, lemon juice, citric acid, or ascorbic acid (but not ascorbate, that is a base.) This would certainly make it more powerful. But I must really caution you about that!

Maybe there is a good reason why the company wanted only a minuscule amount of the alpha hydroxy acid to be in the active form. The acids work, scientists believe in part, by breaking down junctions (desmosomes) between dead skin cells. This allows dead cells in outer skin layers to be removed, and it does seem to stimulate growth of cells below, and their manufacture of water-attracting molecules like hyaluronic acid and reinforcing ones like collagen. But the process can be irritating, and you can end up looking worse than before, with reddened, irritated skin.

You are supposed to apply sunscreen religiously if you use such products, (actually it is a good idea to do so daily, anyway.) The more powerful preparations are applied by a dermatologist, not at home. So although it is theoretically possible to make your preparations more active, I don't advocate placing a lot of active acid on your face without a dermatologist administering them.

Finally, if anyone is wondering why the pH can render an acid effective or ineffective, here are some chemical details:

Alpha hydroxy acids are quite popular in skin formulations these days. They are just organic acids, with a particular structural modification. Let me first show you what any organic acid looks like:

The "alpha hydroxy" designation just means that there is something called a hydroxyl group (O bonded to H) connected to the "alpha" carbon. The alpha carbon of an acid is the carbon that is immediately bonded to the carbon in the square, above. (Sometimes skin products have beta-hydroxy acids, which means that the hydroxyl is bonded to a carbon that is attached to the alpha carbon, the next carbon over.) Chemists use this alpha-beta whatsis language to tell each other how the molecule is constructed and what is bonded to what.

But what makes any organic behave like an acid is the H in the square in the picture. An acidic solution is full of H+ ions, and acids are capable of releasing H+ ions--if they are in the right environment.

But if you place an acid in a more H+ deficient environment, like a neutral or basic one, its H+ is likely to leave, and what is left behind is not an acid anymore, and will not work as an acid.

If you are one of my students, I don't feel comfortable pressurizing you to get my book at all, because that is undue influence, and unethical! But there is a way out of this dilemma. Visit your local public library. There you can borrow a copy for free, and I see that many libraries are now getting it.

Don't you love the library? So often we forget it exists! Support your local library!

It depends. According to clinical studies, alas, pills of parsley extracts including chlorophyll don't work. I think the reason it was once an attractive idea is because theoretically, chlorophyll might stick to some aromatic molecules in your gut, by intermolecular attractions, facilitating their exit through the back passage. But just because you can think of a molecular mechanism does not mean that it works in people. If that were true, all we would have to do is think up mechanisms and we wouldn't have to do any experiments! In any case, swallowing the stuff does not seem to work.

Chewing parsley leaves, on the other hand, mechanically scrapes your teeth and helps remove potentially stinky or otherwise unsociable food bits from them. This is similar to chewing sugarless gum. This is nice if you don't have a toothbrush handy. Clean, washed parsley sprigs make a nice healthy snack, anyway.

Popping any sort of parsely or chlorophyll pill, on the other hand, does not seem to work according to human studies. And I don't think the placebo effect will help you where halitosis is concerned.

Can you tell me if capsaicin creams that I keep seeing in my drugstore work for pain? All I know is that peppers burn my skin! Why would people put this on their skin? How is it supposed to work? I am scared to try it until I know how it works.

S. L. A., Georgia

Dear S.,

You are very wise to want to know how something works before you try it!! Your curiosity can save you. I hope your curiosity is contageous!

Red pepper creams do indeed work for some kinds of pain. Isn't that remarkable? In a nutshell, they are thought to work by quickly depleting your nerves of a pain signaling molecule called substance P. As one of my pharmacology students once neatly put it, "It's a substance P dumper". The real trick is to not use too much of it or to apply it to any sensitive parts!

Here is more detail on red pepper, from my book:

Red Pepper

Capsicum annum or Capsicum frutescens

History and Folklore Also called capsicum, chili pepper, and cayenne pepper, red pepper is a member of the Solanaceae family of plants, and is native to South America. (Black pepper is an unrelated plant from Africa.) The ancient version of these peppers was small, spicy berries. As early as 7000 BCE, South American Indians, perhaps on the basis of a dare, started using them in cooking. Until European explorers brought this tropical plant to India, Africa, China, and Indonesia, the traditionally hot meals of these countries did not include red pepper, which is difficult to imagine.

Different cultures developed new varieties, from the mild Hungarian pepper (paprika) to the fiery South American Habanero. Botanists have recorded over 90 varieties.

Think about the difference between the customary foods of hot and cold countries. The spiciest meals are in the hottest countries, but why?

Some say spicy food helped residents sweat, cooling them off. Yet sweating doesn’t normally require encouragement in heat. The habit of adding plants with violent tastes to food was much more likely a means of preserving it without refrigeration. Food refrigeration using methods prior to refrigerators—ice and cold running streams—wasn’t much of an option in the tropics. The only other convenient means of preserving food is to dump some spicy antibacterial herbs into it. Most spices’ pungent oils are manufactured by plants to keep microbes from attacking the plant, so the antibacterial activity of herbal oils is widespread (but usually too nonspecific to pay much attention to.) The presence of abundant red pepper and other spices discouraged the growth of bacteria, at the risk of discouraging the diner. There was an added benefit: Should the spices fail to retard spoilage, they could still mask a rotten taste.

Red pepper was also used to relieve indigestion and gas, to relieve sinus congestion, headache, and muscle pain. It also has a reputation of being an aphrodisiac (but don’t try it for that use topically, it will probably backfire.)

What’s in it Red pepper oil contains capsaicinoids, alkaloids that resemble vanillin from vanilla, oddly enough, yet an 8-10-carbon hydrocarbon is tacked on to the completely reduced aldehyde carbon of vanillin using an amide linkage. Most of these are capsaicin (32-38%) and dihydrocapsaicin (18-52%). The carotenoid pigments include carotene, capsanthin, alpha-carotin, and violaxanthine. Apiin and luteolin glycoside are the major flavonoids, and the mixture of steroid saponins in the seeds are collectively called capsicidine. The pepper also has a significant amount of vitamin C.

How Scientists Think it Works

Even without taste buds, red pepper would still burn your mouth. When you eat red pepper, you do not actually taste capsaicin with your taste buds. Like other oil-soluble, small molecules, it has the ability to penetrate tissues. It slowly moves through tissues in your mouth, to trigger deeper nerves, and the classic burning sensation slowly grows. Since humans can detect one part per million, a little bit goes a long way.

Paradoxically, it relieves pain, but it isn’t your usual counterirritant. This painful plant is used topically very carefully for pain relief, and it seems to work. At first scientists provided the classic old “counterirritant theory” to explain why: you are so distracted by the pain caused by the herb that you forget your original pain. This is sort of like hitting your thumb with a hammer so you can forget your headache, and you can imagine how appealing this sort of treatment is once someone grasps how it works. Some counterirritant action may in part explain how red pepper works. However, experimenters have unearthed a far more promising mechanism.

The capsaicin in red pepper fools your brain into sensing heat when there isn’t any. Acting just like one of your own neurotransmitters, capsaicin (cap-SAY-sin) binds to a nerve receptor called the VR1 receptor, and temporarily changes the shape of the receptor. The VR1 receptor is ordinarily deformed by heat above around 42 oC (108 oF) and its change in shape opens the nerve cell’s gates to charged particles called ions. Ions then flood into the nerve cell, producing a signal to a second nerve. The signal travels from nerve to nerve to reach the brain, and pain, perceived as heat, is felt. You think you’re are hot, but you’re not. You even respond as if you are hot, for example, it makes you sweat. (VR1 stands for “vanilloid receptor 1”. Oddly enough, capsaicin looks like the vanillin in vanilla, except it has a modification that makes it more fat-soluble. Obviously it doesn’t taste like vanilla.)

Capsaicin relieves pain by depleting your nerves’ supply of substance P, the “bad pain” neurotransmitter. Physicians classify pain as “good pain” or “bad pain”. Although you might find it hard to admit that any pain could is “good,” in fact, the short-term (acute) pain that you feel when you accidentally rest your fingers on a hot stove instructs you to jerk your hand away before it is burnt to a crisp, so it is good. “Bad pain” is long-term (chronic) pain, and is mediated by a different neurotransmitter than the one that signals good pain. Nerves that send good pain signals are fast, but nerves that send bad pain signals are slow, and they generate chronic, long-term pain. The bad pain neurotransmitter is called substance P (the “P”, of course, stands for pain). Capsaicin causes your bad pain nerves to deliver off their substance P to other pain nerves up leading to the brain in a big way. The bad pain nerves lose so much substance P all at once that they are depleted of this molecule, and are unable to release any more. Initially pain is felt, but after the substance P supply is dumped, the nerves are no longer able to send a pain signal to the brain, because they are all out of substance P, and don’t have time to make any more.

(Capsaicin binding to VR1 receptors triggers the release of the bad pain transmitter, substance P, initially, but substance P does not bind capsaicin’s VR1 receptors. It binds NK1 receptors, as it travels up to your brain, and new therapeutics blocking NK1 receptors may also prove another method of relieving pain. Incidentally, the dominant neurotransmitter signaling “good pain” is glutamate.)

Whether capsaicin helps depends; are you feeling good pain or bad pain? Bad pain nerves signal slowly, because they are poorly insulated—insulation along segments of nerves in vertebrates allows the signal to jump faster, from gap to gap in between each insulated segment. With less of this signal-accelerating insulation, bad pain signals build slowly but take a long time to die down. These are the same slow signaling nerves that are active in arthritis and other types of chronic, painful conditions, and capsaicin seems useful in dulling this pain.

Fast nerves are more heavily insulated, and conduct good pain, which is felt only briefly. If you burn yourself lightly on a stove and your bad pain nerves don’t kick in to join the slow ones’ complaint, capsaicin may not help your “good” pain get any better.

A new discovery reveals your brains are spicier than you think. You don’t have capsaicin in your brain, but you have similar-looking molecules called endogenous capsaicin analogues. You even have VR1 receptors in your brain for them to bind, but we aren’t exactly sure of all that happens when they do. It seems they are used to signal to you brain that something is wrong in your body, and they enhance your perception of pain. For example, VR1 receptors on the heart were recently discovered, too, and the way you feel a heart attack coming on is your own versions of capsaicin bind to these receptors on your heart. They may have other physiological effects as well, like on blood pressure and respiratory airway constriction.

Capsaicin could point us toward a brand new class of pain relievers. Researchers are currently at work using this information to produce a new class of VR1 receptor blockers as painkillers. Unlike traditional painkillers that work like aspirin or morphine, they could theoretically address pain more directly, and have fewer side effects. One called capsazepine, for example, kept rodents from feeling certain types of pain stimuli. Because these antidepressants resemble capsaicin, they are called “capsaicin analogues.” While it will be exciting to see what drugs researchers can synthesize to relieve our pain in new ways, the red pepper plant has beat them to it.

Good Uses…And Not So Good

It’s nutritious if you can stomach it. The red color of the peppers is from carotene, the same plant pigment molecule that makes carrots orange. Carotene is used by our bodies to make vitamin A, and red peppers are also a surprisingly good source of vitamin C: one small pod red pepper pod contains more vitamin C than a cup of orange juice.

Red pepper can burn you twice. Capsaicin is not chemically altered by your gut, after it is eaten, and any extra capsaicin you do not absorb retains its burning power all the way toward the bitter end. Thus excessive capsaicin can induce a painfully unpleasant bowel movement. Doctors have invented the term “jalapeno-proctitis” for this unpleasant phenomenon.

Here’s how to remove it from your mouth and other painful places. The first step is preventing yourself from having to do this in the first place. Cooks recommend wearing rubber gloves to handle red peppers. If you get it on your skin and it’s too much for you, first try cold, not hot, soapy water. (Heat will deform your VR1 receptors even more, which is what the capsaicin is already doing.) Then, since capsaicin is oil soluble, try fatty, oily things to remove it. This will work if your mouth is burning, too. There are anecdotal reports of using milk, but it might not work so well with skim milk. Buttered bread is another folk remedy, but could work in theory because of the butter. Beer is also supposed to help—if you have your beer cold, anyway, so beer could anesthetize you beyond it’s traditional mode of action.

Substance P makes your nose run. Substance P is more than a pain neurotransmitter. It stimulates inflammatory processes, and if you eat enough red pepper, the consequent substance P dumping inflames your nose a bit, making it run. Some turn this to their advantage if they are congested, and thus it is included in folkloric cold remedies.

For topical pain relief, a prepared product is probably a safer bet than doing it yourself. You can now find these in your standard grocery store. The FDA has approved the use of over-the-counter pain-relieving topical creams containing up to 0.075% capsaicin. Higher concentrations can cause unpleasant burning, making you feel even worse. Although testimonials are never a guarantee of anything, I’ll submit that my own first experimentations with applying these creams very lightly to my sore muscles following weightlifting definitely helped reduce pain to a degree that surprised me. One medical reference(1) tells doctors to advise their patient that they can wash off the cream with watered down vinegar if they dislike the effect.

Watch wear you put it. Since care must be taken not to introduce capsaicin into cuts, wounds, the eyes, or mucous membranes, some preparations come with a ball roller, stick applicator, or patch, to minimize this risk. Some do not, however. Anyone who accidentally transfers a little red pepper under the fingernails to a more delicate area of the body is unlikely to forget the painful result. It’s better if you don’t use your fingers to apply capsaicin creams, anyway, or at least keep track of which finger you’ve used, and watch wear you put it, later. Even after washing your hands thoroughly, a trace left on your fingers can remain for hours and be transferred to your eyeball if you change your contacts lenses. The result is agony.

It could keep your feet warm. Some winter sports enthusiasts sprinkle red pepper powder in their socks, as this reportedly keeps feet toasty; now red pepper powder is being sold commercially for footwarming purposes. My mother, who suffers from poor circulation in her feet, testifies that this works, but also warns our family not to contaminate your underwear drawer with socks that have been used for this purpose.

Interesting Facts There are some fascinating, new, non-medical products being made with capsaicin, as well. For example, capsaicin incorporated inside veterinary sutures can prevent pets from gnawing off their stitches. And a new capsaicin spiked paint is being tested on fiber optic cable, to prevent the cables from being chewed by rodents. The paint has even been used on boats to repel barnacles.

Capsaicin could also keep competition for your birdfeeders by creatures other than birds to a minimum. In a red pepper eating contest, even the most macho, curry-guzzling, salsa-swigging braggart would be knocked out of first place by a bird. Although mammals are affected by capsaicin, birds are not. They have a different type of VR1 receptor. The bird VR1 receptor responds to heat, but is indifferent to capsaicin. Birdwatchers have observed birds nonchalantly dining on red peppers, and later these birds deposit the undigested seeds, facilitating the plant’s distribution. Some inquisitive birdwatcher got the idea to lace their birdseed with capsaicin. This red pepper-birdseed mix is now sold commercially. Birds happily eat the seed, while rodents avoid it. The capsaicin-eating birds reportedly suffer no adverse effects. Indeed, the trace carotenoids and vitamins in the spice is said to give them extra pep.

Evidence of Action Well-designed clinical trials have repeatedly confirmed that topical red pepper creams are indeed quite helpful in treating a number of painful conditions, including rheumatoid arthritis(2), osteoarthritis(3), as well as neuralgias like shingles(4), and diabetic neuropathy(5). It also proved effective treating lower back(6) pain, and in a preliminary pilot study, chronic neck pain(7). It could possibly help those with fibromyalgia, but more study is required to confirm this(8).

A few people in these studies do not tolerate the treatment, and some have especially adverse reactions to it. Others had to apply the cream several times a day for a week until they noticed positive results.

Red pepper apparently generates indigestion in some people, but relieves it in others. For people who suffered ordinary chronic indigestion (without gastrointestinal reflux disease or irritable bowel syndrome), red pepper significantly reduced discomfort(9). On the other hand, another study shows in people who routinely had heartburn, it made their heartburn more painful(10).

There is some controversy over eating red pepper for ulcers. It could theoretically help, and endoscopies proved capsaicin significantly protected people who did not have ulcers from aspirin-generated stomach injury(11). Some have suggested it might help ulcer patients by killing the infecting Helicobacter bacterium frequently associated with the ulcers. Even though red pepper has bacteriocidal activity in the test tube, most herbs do, and you have to be careful extrapolating test tube studies to people. When people with Helicobacter-associated ulcers ate red pepper, it did not have any effect on their infections(12). It may yet still help ulcers by other mechanisms, but more data is needed to render a conclusion.

· Red pepper creams can cause painful burning sensations if applied too liberally, or to sensitive areas like the eyes and mucous membranes.

· Through it’s substance P-depleting mechanism, red pepper may help certain types of indigestion, including ulcers, but make other kinds of indigestion worse, like heartburn. More experimental data is needed to support the effectiveness of this treatment.

· Humans make molecules similar to red pepper’s capsaicin. Blocking their action may lead to the invention of a new class of pain medications.

I have heard that guarana doesn't have caffeine, but something else that stimulates you. Is it just the sugar in guarana drinks? How does it work?

R. T., Costa Rica

Guarana, the plant, contains caffeine, and this is identical to the caffeine in coffee, tea, and cola. I love to talk about caffeine, because it is one my own favorite plant derived molecules, and it isn't as bad as people think. Societal opinion about caffeine is a classic case of people making a snap judgements prior to more thorough scientific investigation.

People also have historically assumed that sugar revs you up, perhaps because we intuit it can be used for energy--but we don't necessarily use it for energy. Sugar can also be stored (as either glycogen or fat). Once again, science is showing we can't trust our first opinions: sugar, or carbohydrates in general may even have sedating effects for some.

Here are some excerpts from my book on how guarana works:

Guarana

Paullinia cupana, Paullinia sorbilis

History and Folklore If you are from South America, you already know all about this herb. I was introduced to guarana ages ago, through a spell-checker.

Fumbling about as a novice on one of the very first word-processing software programs available, I was writing a letter to my Norwegian sister in law, Jurene. Pressing the wrong button, I was startled to see her name changed to Guarana in every instance. “Dear Guarana,” the letter now began. “What on earth is that?” I wondered, irked that the demonstrably dim spell-checker knew more words than I did. I had to look it up. I learned my spell-checker believed my relation was “an invigorating South American shrub”.

I have been further educated by my Brazilian students that guarana is the national drink of Brazil, and, eyes gleaming, they proclaim absolute devotion to it. As an unabashed coffee lover I can relate—its main therapeutic constituent is caffeine.

Guarana is both a climbing, Amazonian evergreen vine, and the drink made from its seeds. Indian legend holds the plant grew from the eyes of a divine child that was killed by a serpent. Guarani Indians were the first to process the seeds, hence its name. After the seeds are shelled and roasted, they are powdered and mixed with water to form a dough. This is molded into hard cakes or bars. Amazonian Indians used these on-the-go guarana bars by grating off a piece for themselves with a hard fish bone when they needed a little extra zip. This form of guarana is likened to bitter chocolate, only astringent and dry, without the fat found in cocoa butter.

Besides abating fatigue, guarana is considered an aphrodisiac. Traditionally it is used to treat mild digestive upset—its tannins may help in that arena—and headache—an action probably assisted by its caffeine.

Guarana seeds are also mixed with cassava and allowed to ferment to make one of Brazil’s favorite drinks. Sugary, amber-colored guarana sodas, however, are huge in South America, and most of its devotees say it’s not just the caffeine but guarana’s contribution of an unusual, spicy, berry-like flavor not found in other sodas. These have made their inroads into U.S. grocery shelves, marketed under the term “energy drinks”, and sporting confidence-inspiring names, like “Bawls”.

What’s in it Guarana contains the stimulant purine alkaloids caffeine (2-7.5%) and smaller amounts of theophylline and theobromine. Its tannins are proanthocyanidins (12%), and also contains cyanolipids such as 2,4-dihydroxy-3-butyronitrile. It also contains trace amounts of the saponin fish poison timbonine.

How Scientists Think it Works

Guarana’s main active ingredient is caffeine. Like tea, coffee, cocoa, and mate’, these unrelated plants all possess differing amounts of stimulant molecules called methylxanthines: the classic stimulant trio of caffeine, theophylline, and theobromine. They all tend to work the same way, with different potencies and subspecialities. Caffeine is the most prominent one in guarana, and guarana has more caffeine than coffee. People taking guarana typically experience the same effects as those drinking coffee.

You may already be familiar with caffeine’s most obvious effects, like stimulation, faster heartbeat, and an exceptional urge to urinate. Caffeine also stimulates your gut’s release of digestive enzymes and acid, discourages blood clots, and briefly raises your blood pressure, as if you have been climbing a flight of stairs. Regular caffeine consumers, however, do not have high blood pressure.

A lot of caffeine’s other effects are signature moves of the “fight or flight” nervous system. This readies you for action, and some of these effects can be exploited therapeutically. For example, blood vessels in muscles are widened, allowing them greater access to blood sugar. At the same time, blood sugar is released from stores in the liver, and fat breakdown is stimulated (hooray!), the products of which can also be used to feed cells poised for action. Caffeine tends to suppress appetite—eating is not something you need to do while fighting or fleeing—plus its stimulating effects form the rationale for its addition to diet aids. Blood vessels in other areas are constricted, like in the brain and skin, conserving its delivery to muscles and lungs. The constriction of blood vessels in your brain by caffeine makes it useful in treating vascular headaches, and you may notice its addition to some over the counter analgesics and prescription migraine medicines. Caffeine opens up the respiratory system, allowing you to get more oxygen. Theophylline, one of the other methylxanthines, is better at this than caffeine, however, and is therefore used in asthma medications.

How does the caffeine in guarana and other plants perform these tricks? Caffeine is an adenosine receptor antagonist. The main effects of caffeine are attributed to its antagonism of a molecule called adenosine. Caffeine does other things, too, like increasing calcium in muscle cells, making them twitchy by lowering the threshold stimulus needed for them to contract. Caffeine may also stimulate histamine receptors in your gut, too, increasing digestive juices. But the main effects of caffeine are through its inhibition of a sleep-inducing molecule called adenosine.

Adenosine is released as part of a larger molecule called adenosine triphosphate, or ATP, from stimulatory nerves, but it doesn’t stimulate. It is released at the same time as the stimulatory fight-or-flight neurotransmitter, norepinephrine, perhaps as a means to keep norepinephrine from getting out of hand. The slow, spontaneous breakdown of ATP lingering outside the nerve releases adenosine. This adenosine doubles back on its tracks, and binds to adenosine receptors on the nerve that released it.

Adenosine blunts the nerves’ ability to release the stimulatory norepinephrine, so adenosine inhibits brain activity, and it makes you sleepy. Adenosine also accumulates throughout the day as ATP is broken down during its use to fuel reactions that just would not go on their own; reactions that require energy.

So, as you spend energy throughout the day, adenosine builds up, and it’s binding to adenosine receptors in your brain shuts down your brains’ activity.

Caffeine and other methylxanthines look a lot like adenosine, and also temporarily stick to adenosine receptors, blocking adenosine’s access to them. This keeps you from getting sleepy. Besides allowing the fight-or-flight stimulant norepinephrine to work unopposed by adenosine, caffeine has indirect effects that boost dopamine and serotonin, and this could explain why we get a pleasure-enhancing mood reward from consuming it.

Scientists speculate that caffeine’s effect on these hormones may explain why large studies have shown that habitual caffeine consumers are less likely to get Parkinson’s disease or to commit suicide. Despite our puritanical impulses to portray anything that makes us feel so good as a danger, caffeine has several health benefits, although certain people should not have it. For a summary of all of caffeine’s positive and negative disease risks, see “interesting facts”, below.

Guarana also contains a lot of tannin. The effects of guarana tannin are less well known. Small doses of tannin are benign and can even be helpful. Tannin cross-link proteins, pulling them tight, and this skin-tightening effect is meant by “astringent”. Tannins “tan” the lining of your mouth and digestive tract in a mild way. This forms a temporary, protective barrier against gastrointestinal irritants, hence guarana’s traditional use in treating indigestion. Large doses, however, can upset your stomach.

Unlike mate', guarana is not (so far at least) linked to increased cancer risk. Another tannin-containing South American herb, yerba mate’ (see also), is very popular and part of South American cultural traditions, just as wine drinking is among European ones. Like guarana, it has both caffeine and a high tannin content. Mate’, however, has been repeatedly linked to an increased risk of certain cancers, and we aren’t sure why. It certainly isn’t its caffeine content. Early studies suggesting caffeine was a carcinogen were confounded by coffee drinkers’ tendency to smoke.

Caffeine has been vindicated of these charges in numerous, better-designed studies, and the American Cancer Society officially states that caffeine does not cause cancer. Tannin, on the other hand, theoretically could, if you have loads of it, and some have proposed this is behind mate’s’ increased cancer risk.

There have been no associations of guarana with cancer, but no one has performed epidemiological cancer-risk studies on it, either. If you want to limit any tannin’s actions, have it with protein. The tannin reacts with the protein and not with you.

Good Uses…And Not So Good

Guarana gives you an energy boost, and can stop a vascular headache, but don’t overdo it. Too much stimulation will make you jittery and bad-tempered, and any fine motor controls you require go down the drain. I’ll never forget being impressed by the latter effect, staying up late doing lab work, drinking coffee, and discovering that my hands under my microscope magnified their tiny caffeine-induced tremors into awesome, large scale oscillations. It dawned on me as the explanation for my clumsy work, and I sadly pitched my coffee in order to continue my microscopy. If you do fine artwork or anything requiring careful control of your hands, don’t have guarana beforehand.

Watch out for withdrawal. Like other caffeine containing beverages, guarana is pleasure-enhancing and addictive; though this is not as sinister as it sounds. The tolerance you develop to caffeine is mild, and unlike many other additive drugs, caffeine pharmacology works differently. It isn’t something that you need more and more of to continue having the same effect. You won’t end up selling your house and car to fund your caffeine habit, for example.

There are health benefits to moderate regular caffeine drinking, too though not everyone should have it. It you are used to guarana or other caffeinated substances, their sudden withdrawal may cause blood to flood into your brain, causing headache, and the increased number of adenosine receptors that you make while taking caffeine makes you more susceptible to adenosine’s sleep-inducing effects, making you groggy.

Certain people should limit their guarana. It is not for the insomniac. Caffeine is a common culprit in causing insomnia, and guarana’s caffeine content is higher than coffee’s. Caffeine can cause some people to have an irregular heartbeat, and if you think you are one of these people, don’t have guarana. Certainly, if you don’t like how it makes you feel, don’t take it! If you are not a regular consumer of caffeine, it may boost your blood pressure, though those who take it regularly don’t experience this effect. Because caffeine can enter fetal circulation, pregnant women are advised to have no more than one cup of coffee per day, and since guarana has more caffeine, guarana abstinence seems wise. Unless you want a fussy, sleepless baby, don’t nurse while taking guarana, either. The caffeine in it is transported through breast milk.

Guarana is not for pets. Although the problem is more often seen with chocolate, pets should not be exposed to methylxanthines in general, because they resond differently than humans and in some cases it can kill them.

Various forms of guarana have precautions, too. The diet and cognitive aids containing guarana typically contain many other herbs with unknown safety records, and since it’s not clear they work, avoid them. And although there are some “diet” versions, most guarana sodas and “energy drinks” are brimming with sugar. Since energy is measured in calories, why not rename them “calorie drinks”? Their sugar can certainly make you gain weight. Sugary sodas cause tooth decay, too.

The tannins in guarana are an unknown, but a concern. It is not known if their presence in the herb mate’ causes cancer, for example. Tannins do limit your absorption of protein, because they bind to proteins in your gut. To limit the action of tannins in your gut, some have suggested taking high-tannin containing herbs like guarana with milk, to keep them preoccupied enough with milk proteins.

Interesting facts: Through caffeine, nature teaches us once again that no molecule is entirely bad or entirely good. Regular caffeine consumption has been associated with a decreased risk of committing suicide, and less risk of developing Parkinson’s disease, gallstones, liver disease, and type 2 diabetes. On the other hand, it can increase urinary loss of calcium, although studies attempting to link it to osteoporosis have been inconclusive, perhaps because dietary calcium compensated for the loss in the people studied. It was once believed caffeine stimulated breast cyst formation, but this is no longer held to be true; well-designed studies have found no evidence to support this. Caffeine can cause some people to have an irregular heart beat, although it is not associated with causing heart disease. It can enter fetal circulation and its effects on fetuses are unknown, but not associated with birth defects. However, a Danish study found that women consuming more than 300 mg of caffeine a day were more likely to risk a stillborn child, so pregnant women should limit it or avoid it entirely.

Evidence of Action There are not many studies of the effects of guarana on humans. Its effects on cognitive performance are contradictory. One double blind study says it had no significant effect on elderly volunteers compared to caffeine or placebo(1), while another double blind placebo controlled study suggested guarana gave participants moderately better attention on mental tests, but slightly worse accuracy in their answers(2).

Two studies examine guarana as a weight loss agent, but unfortunately, mixed with other herbs, so it is hard to say which herb is doing what. Healthy volunteers consuming guarana mixed with yerba mate’ and damiana, showed significantly delayed gastric emptying compared to placebo, theoretically helping them retain a feeling of fullness(3). Mice fed solely guarana, or caffeine, however, showed no change gastrointestinal transit, in another study(4). After 45 days of taking this mixture, significant weight loss of around 11 pounds (5 kg) was seen, and for those who continued on the extract for a year, the weight was not regained.

Another mixture containing guarana and the now widely banned ephedra showed significantly greater loss of weight and fat than those taking placeboes(5), but it should be noted that 11 of the 35 subjects in the active group withdrew before the study was complete, complaining of chest pain, heart palpitations, increased blood pressure, and irritability, and it is likely that a lot of these side effects were caused by ephedra, which was banned for its toxic and sometimes fatal effects on the heart.

Guarana contributes caffeine, which is an appetite suppressant and stimulant, and this theoretically could have contributed to the effects in these studies. However, there is no way to tell whether guarana caused the weight loss in these studies of herbal mixtures.

Caffeine also stimulates an increase in blood sugar, blood pressure, and heart rate, all of which were significantly elevated in the later studies’ herb-taking volunteers as well. Mice fed guarana also experienced a significant surge in blood sugar after an hour, from its storage form, glycogen, in the liver(6). This significantly prevented them from experiencing a drop in blood sugar during exercise. Rats fed guarana had better endurance in swimming tests, and showed no ill effects from the herb(7).

Animal studies hint that guarana isn’t harmful, and it could provide certain health benefits. A study with rabbits fed guarana showed their platelets were less likely to clot(8), a known effect of caffeine. Guarana also prevented chemical induced liver cancer in mice(9), and protected rats from indomethacin or alcohol caused stomach injury(10). No toxic or adverse effects of guarana on behavior or organ tissues of rats or mice were seen even at high doses(11). Additionally, an antioxidant effect was observed in the form of decreased membrane oxidation (lipid peroxidation.)

The Bottom Line

· Guarana exhibits therapeutic actions through its high caffeine content. Caffeine works primarily by blocking a sleep-inducing molecule called adenosine.

· Because of its caffeine, guarana is a stimulant, and can be effectively used to treat vascular headaches. It is not clear whether it boosts mental ability or works as a diet aid, however.

· Guarana also has tannins, which in small doses can relieve indigestion, but in large doses can cause it. The high dose of tannins from another stimulant South American herb mate’ might increase cancer risk, but no one knows whether guarana is associated with cancer, as well.

· Although regular, moderate caffeine intake is associated with health benefits, it should not be taken in excess, it can cause withdrawal, and certain people should not have it. People prone to irregular heartbeat and pregnant or nursing women should avoid guarana.

Hi, I have a question regarding parsley. My blood pressure is low and lastweek I fainted, since I was on my period too. Do you think parsley canbalance my blood pressure? Also, my white cell counts are slightly morethan my red cell counts.Please advise, E. G.

Hi E. G.,

I doubt very much that parsley will affect your blood pressure or blood cell counts to a significant degree, if you have a metabolic problem.

If your red blood count is very low, you should definitely see a doctor and try to pinpoint why, since there are different causes of anemia. More blood tests should be taken to see if you have too little vitamin B12 (some vegans have a problem with that and some people with digestive problems may have trouble absorbing it) or too much or too little iron (due to a metabolic problem or diet).

Normally people don't worry about their blood pressure being too low--they worry about it being high! I was going to joke that if you wanted to raise your blood pressure all you have to do is eat salty fast foods and watch the political news, but please don't do that!

But your blood pressure is abnormally low and you are fainting or feel faint a lot, again you should have it checked out. It is too complicated an issue to sort out over the email. It is the sort of thing that an herb is not likely to impact to any great degree, but of course healthy diet and living will help.

Of course, herbs that raise your blood pressure are not a good idea, they could be dangerous.

If your red blood cell count is as low as you say, or your white blood cell count as high (you didn't give me numbers so I am not sure) you really need to find out what is going on with more blood tests. I hope you can find a dr. you like who you can trust.

I hope that helped a little bit at least, and I am glad to see that you are interested in caring for yourself--you are wise to pursue this.

I have multiple food sensitivities, and I don't think my physicians have a clue. I think

parsley's "antinutritional" constituents and other antinutritional constituents of edamame beans, green peas, various raw vegetables, garlic, Chick peas, in a meal I had last night produced a mild or not so mild laxative effect. I think that I'm sensitive to antinutritional properties in foods and have no idea how to figure this out and how to get good nutrition. Mine is a long story and all I meant to do was to thank you for your informative article.

Chris

Hi Chris,

I am so glad you found my parsley chapter informative. Thank you for the positive feedback!

Yes, we are all very unique creatures, and what helps one person can send other into agony. You might want to keep a food diary for a while to see how you are responding to various meals.

Unless you had a ton of parsley, I suspect it may more likely be all the fiber you had that cleaned you out, so to speak. Fiber is a great thing but it takes some getting used to. And some types of plant fiber are easier to digest than others. For example, you had edamame, or soybeans:

Soybeans can be particularly troublesome for some, for they contain short sugar chains that, should they make it all they way to your colon, are digested vigorously by colonic bactieria, which in their own small way emit an astonishing amount of gas, which we must deal with in a larger way.

For food sensitivities, you have to be a real detective, and the data you get on yourself can be confusing: there are so many variables to test, and you are just one person with no control group!

Don't jump to any permanent conclusions too quickly. The best scientists and detectives are always kicking the tires of their own beliefs and testing them until they know they are well supported by evidence. It may be a good sign that your doctors can admit they do not know. I would be less trustful of those who claim to have all the answers.

Doctors recommend (I am not an MD, just a PhD scientist) for assessing food sensitivities omitting just one particular suspected food item for a few weeks, and then reintroducing it to see if it really does make you feel sick. The most common culprits for food sensitivities are:

cereals based on wheat and corn, dairy products, peanuts, nuts, soybeans, and shellfish.

Your doctors can also take some of your blood to test for wheat gluten sensitivity, which is surprisingly common. This test is not 100% accurate, but can be confirmed with endoscopy.

Hi—love your site! I’m an MD/PhD student in the Bronx, and I have a quicky catnip question for you. I’ve read your Jan 20 ’04 post, and like most of the sources I’ve found on the internet so far, it mentions the vomeronasal organ as the site of action of catnip, attributing the smell of the substance as what the cats are after. Do you know of any research showing catnip receptors inside cats’ brains? I guess because the vomeronasal organ in humans is nonexistent, I’m just having a hard time wrapping my mind around the idea of the smell itself of a substance being the only mechanism behind such a consistent, stereotyped behavior across individual animals, without some sort of direct action inside the brain itself. But I guess that’s why I’m not a cat. ;) Thanks for your help!

C., Albert Einstein College of Medicine

Hello and thank you! I am so glad you enjoy my website.

You know, I have searched all over several scientific databases, but I can't find any reputable articles on catnip or nepetalactone's (which is 80-95% of catnip oil) interaction with human or cat brain receptors. There is an article (Aydin et. al., ) suggesting interactions with rodent brain opioid receptors. But you are absolutely right, it does bind to receptors in the cat's VNO, or vomeronasal organ.

As you already know, the existence of this pheromone sensor in people's sniffers has been hotly debated. But cats have it, and I am guessing that once nepetalactone binds its receptor in cat's VNO, the VNO then sends signals to the cat brain. So, your question is really, where do those signals go? I don't know...but hopefully no one will discomfort any cats to find out.

Some cats also love the herb valerian in the same, silly way, and it has valepotriates, chemicals that resemble nepetalactone. One of our own cats, Alberio, LOVES to stick her nose in our peppermint tea, regardless of brand, and ignores all our other herbal teas. I have not seen other cats do this. Since catnip is a mint, I wonder if Alby has a VNO receptor mutation which causes her to respond to similar molecules in peppermint. She is an odd little thing, psychologically, so this seems not out of the question.

There is evidence that suggests that humans actually respond to pheromones, but where are our VNOs? These organs in other animals respond to sex hormones, and also respond to simple "come here" or "go away" pheromone messages. But the dogma is that we humans don't have a VNO in our noses. Not wanting to feel left out at the animal pheromone party, I suppose, the hunt has been on to find our VNOs.

One new idea is that we humans sense pheromones with our mundane little noses. But scientists have not completely ruled out the possibility of human VNOs existing, either. (Besli et. al.,Wysoki et al., Zosel et. al.) There are traces of them, but their efferent nerves appear to dead end and fail to reach the brain, from what I understand. Failing that, to my mind nepatalactone so resembles valepotriates in valerian, that I have to supsect they could do the same thing, and possibly sedate us by enhancing the binding of the inhibitory neurotransmitter GABA to its receptor.

Why Doesn't Cooked Nettle Sting?

In your article on Nettle, you say that cooking it keeps it from stinging. Why is this?

Dr. J. P., Salt Lake

Oh, what an excellent question! And shame on me for not addressing it in my article. Since I can't find a readily available scientific explanation, I will give you my best guess.

The simplest explanation is that heat causes the stingers to poop out their inflammatory contents, which then get diluted by the rest of the cooked material. Since they are dilute, they are less potent. Realize that a nettle stinger injects a teeny tiny area of your skin with a relatively concentrated dose of inflammatory mediators.

Sometimes heating molecules causes them to degrade, that is, to change into other things which don't have the same activity. But I suspect that is not going on with these molecules. Some molecules are more fragile than others.

Also, heating molecules sometimes gives them enough energy to leave the pot, so to speak, and fly around the room! We call that evaporation. If the molecule has a smell, you can detect such escapism when the molecule flies up your nose. But these are not very volatile (easy to evaporate) molecules, so I don't think that is the case, either. These molecules are too attracted to water to want to leave the pot.